Insulin Resistance

What is Insulin Resistance?

Insulin is a hormone that plays a dominant role in regulating various metabolic processes including blood sugar and body fat percentage. Under normal circumstances, this process is highly dynamic and constantly fine-tuned by the body. However, under certain conditions, the body becomes blunted to the regulatory effects of insulin. When this happens, the normal mechanism starts to fail and ‘insulin resistance’ sets in. As a result, blood sugar levels start to climb.

To compensate the body increases its production of insulin, thereby causing insulin levels to rise. When it comes to regulating blood sugar, rising insulin levels are beneficial since it helps keep rising blood sugar under control. However, when it comes to regulating body fat percentage, rising insulin levels spell somewhat of a disaster. This is because the hormone insulin not only makes the body more effective at storing fat but also makes it more difficult to burn fat.

The net effect is that your metabolism effectively slows down.

How is metabolism regulated?

All biochemical processes that take place in the body are initiated and controlled by a complex communication system that relies on messenger molecules that are able to convey biochemical instructions. Examples of messenger molecules are hormones, neurotransmitters and cytokines. Chemicals contained within pharmaceutical drugs or medicinal plant extracts also achieve their results through the same mechanism.

Depending on their design, messenger molecules deliver their biochemical communication either broadly at a high level to a large audience, or more selectively at a local level in a more specific manner. They can also override or overrule each other, as well as strengthen or amplify another’s message.

Metabolism is a complex process which involves the regulatory activity of various different messenger molecules. It is commonly believed that the thyroid gland is in charge of this process. This misguided view is based on oversimplification, since the numerous regulatory tasks that insulin performs relating to carbohydrate, protein and fat metabolism, as well as how insulin overrules virtually all other messenger molecules involved in the process, makes insulin the single most dominant controller of metabolism.

What causes insulin resistance?

Whilst genetic makeup, increasing age and certain disease states make you more prone to developing insulin resistance, lifestyle factors that lead to weight gain and the ultimate triggers. These include diet and a sedentary lifestyle. At the heart of the problem is excess body fat, not because of the space that it consumes within the body, but because excess body fat starts to release a range of messenger molecules that not only initiates a pathological communication process within fatty tissue itself but as a secondary consequence, spreads a message that usually results in disease to the rest of the body.

Why excess body fat causes insulin resistance

Two major mechanisms contribute towards weight gain. Not only do existing fat cells increase their fat content, but new fat cells are continuously being formed through a proliferation process. Individually, newly formed fat cells also start accumulating fat which collectively leads to accelerated weight-gain and the progressive enlargement of the total fat mass. In a more advanced state, this process leads to the distortion of fatty tissue, commonly referred to as cellulite.

In the past, fat cells were accredited with only two main functions, namely that of storing calories for later use and preserving body temperature via improved insulation. However, in the presence of excess body fat, fat cells also assume a new biochemical communication function by starting to manufacture various messenger molecules including ‘adipokines’ and ‘inflammatory cytokines’. These have an effect on many different tissue types and tend to interfere with the normal chemical function of the body. For reasons not completely understood, some inflammatory cytokines disrupt insulin’s role on a cellular level when it comes to regulating blood sugar, leading to type 2 diabetes.

Adipokines, on the other hand, initiate the process of new fat cell formation called ‘adipogenesis’. In reality, by releasing adipokines and inflammatory cytokines, fat cells, in essence, become an endocrine organ which starts to function independently from the body. A vicious cycle ensues during which you become physiologically and biochemically altered, and you are virtually held hostage by your own abnormal fatty tissue.

Blocking the communication process between fat cells at a cellular level, especially when it comes to the formation of new fat cells and the development of insulin resistance, has, therefore, become a modern therapeutic focus.

Why elevated insulin levels cause weight gain

Insulin performs several different functions that may lead to the accumulation of excess body fat. Firstly, insulin regulates fat production. After a meal, when the quantity of glucose that enters the system is more than what can be used for immediate energy requirements, insulin promotes the conversion of excess sugar into fatty acids. These are subsequently grouped as larger molecules called triglycerides and transported to the fatty tissue where they are stored.

In the body, fat cells represent the ultimate energy store room. Starting life as a miniature pantry, these unique storage containers can rapidly expand in size to fulfil the role of a massive warehouse. Within the environment of fat cells, insulin fulfils the role of storeroom manager. By design, insulin’s tasks are to firstly fill each warehouse to maximum capacity and then secondly, to keep stock levels as high as possible by actively preventing fat from leaving.

Inside a fat cell, however, another messenger molecule called ‘hormone-sensitive lipase’ (HSL) plays an opposing role to insulin. Acting as the dispatch manager of the warehouse, HSL has the sole task of releasing as much fat from the fat cell as possible so that it can be shipped off to fuel the metabolic furnace. In the presence of insulin, however, this biochemical function is overruled and fat effectively stays trapped inside fat cells. Only once insulin levels drop can HSL perform its duty by mobilising and releasing fat from the warehouse.

The bottom line is that insulin not only helps you to gain weight but when levels are chronically elevated as in the presence of insulin resistance, it also makes it more difficult for you to lose weight.

The medical consequences of insulin resistance

Doctors deal with the complications of insulin’s obesity-promoting tendency on a daily basis. Whilst insulin is the critical regulator of blood sugar control, increased insulin levels may also lead to weight gain. In fact, these effects can be rather counterproductive when treating an overweight diabetic patient.

Various studies have confirmed the role that insulin plays in weight gain. This includes data obtained from two landmark studies; the UKPDS (United Kingdom Prospective Diabetes Study) and DCCT (Diabetes Control and Complication Trial). The most obvious example, however, can be seen in someone who develops an insulinoma, a rare tumour of the pancreas that secretes insulin. Besides developing low blood sugar, individuals with insulinomas also gain weight at an alarming rate and can become massively obese in a very short period of time.

In the presence of insulin resistance, limiting insulin-associated weight gain through an insulin sparing mechanism has, therefore, become a novel therapeutic target.

How is insulin resistance diagnosed?

In clinical practice, a combination of fasting insulin and glucose levels are used. These are calculated according to the HOMA (Homeostatic Model Assessment) or QUICKI (quantitative insulin sensitivity check index) method.  In specialised medical research, however, a more accurate technique called the ‘hyperinsulinemic euglycemic clamp’ is used. Research has shown that results from the HOMA and QUICKI correlate reasonably well with clamping studies regarding accuracy.

Although less precise, a more simple way to predict insulin resistance is to measure your waist circumference. According to American guidelines, males with a waistline measurement of more than 90cm and females measuring more than 80cm will be significantly more inclined towards insulin resistance. European guidelines differ slightly from American guidelines, with 93cm for males and 79cm for females being the upper range of normal.

Research suggests that these waist circumference guidelines may be set too high for black South African men, and an even lower cutoff measurement may be more accurate for diagnosing insulin resistance. However, more research is required to confirm this.

How is insulin resistance linked to type 2 diabetes?

Since some of the inflammatory cytokines that fat cells start releasing disrupt insulin’s role on a cellular level when it comes to regulating blood sugar, insulin resistance is one of the leading causes of type 2 diabetes. This escalating process, however, may also fuel a vicious cycle of increased levels of insulin resistance and as a consequence, a greater requirement for insulin, thereby posing the threat of gaining even more weight. Whilst optimal glycemic control is essential to good health, weight gain is also known to accelerate some of the other disease processes associated with the metabolic syndrome, thereby potentially undermining the metabolic and cardiovascular benefits of optimal blood glucose control.

What is the link between insulin resistance and inflammation?

Excess body fat leads to the release of various inflammatory cytokines. In type 2 diabetics, insulin resistance is associated with low-grade chronic inflammation. Since this process is a known risk to develop blood clots in the presence of hardening of the arteries, it is often used to explain some of the microvascular complications that occur in type 2 diabetes. However, there is also significant evidence to suggest that even before the clinical diagnosis of type 2 diabetes is made, those with excess body fat have an increased risk of cardiovascular disease and vascular thrombosis because of low-grade inflammation.

What is the link between insulin resistance and PCOS?

Besides playing the dominant role in metabolism, insulin has a number of other hormonal effects including the regulation of normal ovarian function and influencing a number of male hormones present in females. Increased levels of insulin, as caused by insulin resistance, causes a reduction in a hormone called sex hormone-binding globulin (SHBG) in the liver. This results in abnormally high levels of male hormones in women.

What is the link between insulin resistance and stress?

Various hormones are influenced by stress, especially cortisol, which has been implicated in the development of insulin resistance.  It is also known that insulin resistance and the various inflammatory cytokines that are released by the fat cells during the process can result in far reaching biochemical consequences.  These are known to have a negative impact on brain function, leading to concentration and mental processing problems, irritability and mood disorders, including depression, sleep disorders and dementia.


What is stress?

Stress is the body’s response to a change that requires a physical, mental or emotional adjustment. It is also the body’s method of reacting to or preparing for a new challenge. Stress can originate from any situation or thought that makes you feel concerned, nervous, frustrated or angry. Its effects on the body are not only psychological, but physiological as well.

The physiological reaction that occurs in response to a perceived threat happens via activation of the sympathetic nervous system. This results in a typical ‘fight-or-flight’ response. Besides the nervous system, various stress hormones are also released into the body. The immediate response is activated by the hormones such as adrenaline (epinephrine) and noradrenaline (norepinephrine), whilst cortisol controls the more long-term stress response.

What is cortisol?

Cortisol is a steroid hormone produced by the adrenal glands. Cortisol plays an important role in how the body uses food substrates such as carbohydrate, fat, or protein, in order to meet additional physiological demands. Cortisol is normally released in response to events such as waking up in the morning, during physical exercise and stressful events.

When chronically elevated, cortisol has a negative impact on many systems, including weight control and immune function. With a high stress, fast-paced lifestyle, the body ends up producing cortisol almost continuously. Whilst cortisol is essential to the body, too much cortisol can have a significantly detrimental effect on our health.

What effect does stress have on blood sugar levels and the development of diabetes?

Under stressful conditions, cortisol helps to provide the body with glucose by tapping into protein stores and helping to release the glucose that is stored in the liver. This energy is required in a typical fight-or-flight situation. However, elevated cortisol over the long term constantly stimulates the release of glucose, leading to increased blood sugar levels. Since a principal function of cortisol is to counteract the effects of insulin, it causes bodily cells to become insulin resistant. Over time, the pancreas struggles to keep up with the increased demand for insulin. The result is that glucose levels become elevated. Chronic stress therefore increases the risk for diabetes.

What effect does stress have on weight gain and obesity?

Chronic elevated cortisol levels can lead to weight gain. One mechanism is to stimulate the storage of fatty acids in fatty tissue contained inside the abdominal cavity (visceral fat stores). Another way goes back to the blood-sugar insulin problem. Consistently high blood glucose levels, in the presence of insulin resistance, leads to cells that are starved of glucose. Since these cells are in need of energy, they send hunger signals to the brain via a biochemical signalling mechanism. This leads to increased eating and the intake of excess glucose that is eventually stored in the body as fat. Cortisol has also been linked to cravings for high-calorie foods.

What effect does stress have on the immune system?

Cortisol, being a steroid hormone, is similar to the drug cortisone, often used by doctors to suppress inflammation in virtually all tissue types. In the body, cortisol’s ability to suppress inflammation is mostly beneficial. However, this may also lead to the suppression of the immune system, causing an increased susceptibility to colds, flu and other infections, as well as an increased risk to develop certain forms of cancer. Cortisol is also associated with a tendency to develop food allergies and an increased risk of various gastrointestinal disorders, since a healthy intestine is dependent on a functional immune system. The risk of developing an autoimmune disease is also higher.

What effects does stress have on the gastrointestinal system?

The ‘autonomic nervous system’ is the part of the body’s ‘automatic’ control mechanism that regulates various involuntary bodily functions, such as breathing, digestion and circulation.  It consists of two divisions, namely the sympathetic and parasympathetic systems that, to a large degree, work in opposition to each other. When the sympathetic nervous system is ‘switched on’, the parasympathetic nervous system should ideally be ‘switched off’.

Whilst the sympathetic nervous system accelerates the heart rate, constricts blood vessels and raises blood pressure under stressful conditions, the parasympathetic nervous system does the opposite and helps to slow the heart rate, increase intestinal and glandular activity, and relax sphincter muscles.

The parasympathetic nervous system becomes more active during relaxed activities, such as eating. This is important because for the body to best use food energy, enzymes and hormones controlling digestion and the absorption of nutrients must be working at peak performance. Activation of the sympathetic nervous system by cortisol, however, results in the suppression of the parasympathetic nervous system. This compromises digestion and impairs the absorption of nutrients. As a result, indigestion and heartburn may develop and the mucosal lining of the gastro-intestinal tract may become inflamed. In response, mucosal inflammation of the stomach also leads to the increased production of cortisol, causing a vicious cycle. This is a reason why stomach ulcers are more common during stressful times. Those suffering from irritable bowel syndrome and inflammatory bowel disorders like ulcerative colitis also report an improvement in their symptoms when they master better stress management.

What effect does stress have on the cardiovascular system?

Through the activation of the sympathetic nervous system, cortisol constricts blood vessels and increases blood pressure in order to enhance the delivery of oxygenated blood during the fight-or-flight reaction. Over time, chronic arterial constriction also leads to high blood pressure and hardening of the arteries, which may cause heart attacks and stroke. This is one of the reasons why stressed-out personality types are at a greater risk for developing cardio-vascular disease.

What effect does stress have on fertility?

Elevated cortisol levels relating to prolonged stress can cause the disruption of menstrual cycles and ovulation, resulting in female infertility. Furthermore, the androgenic sex hormones are produced in the same glands as cortisol and epinephrine, so excess cortisol production may impair the optimal production of these hormones. Elevated cortisol levels are also known to cause erectile dysfunction.

What effects does stress have on fatigue?

Long-term stress and elevated cortisol levels are linked to insomnia, chronic fatigue syndrome, thyroid disorders, dementia and depression.

Which lifestyle changes can help to reduce stress?

Seeing that a chain is only as strong as its weakest link, the best way to manage stress is by using a combination of techniques. Start by eating a balanced, nutritious diet. Exercise regularly and avoid poisoning your brain and body with cigarettes, ‘recreational’ drugs and excessive alcohol intake.

Depending on your source of stress, there are various cognitive techniques that can be used to strategically plan, communicate and think better. These include techniques on how to manage conflict more effectively and how to put better boundaries in place between you and the people that cause you to become stressed.

In addition, we recommend the use of a regular supplement to assist you during times of excess work load or emotional fatigue. Roseroot (Rhodiola rosea) is a perennial plant that grows at high altitudes in the Arctic regions of Europe and Asia. Extracts of the roots have been used in Scandinavian and European countries to combat fatigue, reduce the effects of stress and to aid convalescence during illness. Several psychometric tests conducted on subjects under pressure demonstrated a substantial reduction in fatigue-related symptoms and an improvement of various cognitive indicators that are medically associated with increased psychological stress. These include a recorded reduction in cortisol levels. Roseroot has a low side effect profile and is generally considered a safe and effective supplement.


  • DSM IV Diagnostic criteria for acute stress disorder
  • World Health Organisation Guidelines on conditions specifically related to stress, 2013
  • American Institute for Preventative Medicine, General Stress Management, 4th edition 2012


What is Polycystic Ovary Syndrome (PCOS)?

Polycystic Ovary Syndrome (PCOS) is a hormonal disorder that leads to abnormal menstruation, problems with ovary function, cosmetic issues and infertility. PCOS is recognised as one of the most common disorders among reproductive aged women and is considered to be the leading cause of female infertility. By some estimates, one in every five women may meet diagnostic criteria.

Most often, symptoms first appear in adolescence, around the start of menstruation. However, some women do not develop symptoms until their early to mid-20s. Although PCOS presents early in life, it persists through and beyond the reproductive years. In PCOS, there is an imbalance in the hormones that control the menstrual cycle, often in combination with insulin resistance, which then prevent ovulation and decrease fertility.

Importantly, PCOS is not a clear-cut disorder, each person can experience varying degrees of the symptoms below- some may have just one or two while others have many.

What are the symptoms of PCOS?

The main symptoms of PCOS include, and can be varying combinations of:

  • Infrequent, irregular or lengthy menstrual cycles (30–50% have no periods at all)
  • Difficulty falling pregnant and low fertility (>90% are infertile)
  • Heavy bleeding (irregular periods can lead to heavier bleeding when menstruation does occur)
  • Weight gain or difficulty losing weight
  • Abnormal hair growth, often on the upper lip, chin, around the nipples and in a line beneath the navel (60-95% of persons)
  • Thinning hair or male-pattern baldness
  • Acne
  • Darkening of the skin, particularly along neck creases, the groin and underneath breasts
  • Skin tags (small growths or bumps of skin, especially in the armpits or neck area)
  • Ovarian cysts (multiple ‘cysts’, or small, fluid filled sacs in the ovary). Only your doctor can check for this

What disorders are associated with PCOS?

PCOS is primarily a metabolic and reproductive disorder. Specifically, PCOS is very similar to another chronic, metabolic disorder – Metabolic Syndrome (MetS), as well as a number of conditions associated with reproduction. Polycystic ovary syndrome, especially in the presence of obesity, increases the risk of both gynaecological conditions and a wide variety of many other diseases. The main ones are:

MetS associated disorders:

  • More than half of women with PCOS develop diabetes or prediabetes before 40
  • High blood pressure and cardiovascular disease
  • Obesity
  • Non-alcoholic fatty liver disease
  • Chronic, low-grade systemic inflammation

Reproductive disorders:

  • Difficulty conceiving and infertility
  • Gestational diabetes
  • Pregnancy-induced high blood pressure (preeclampsia)
  • Pregnancy abnormalities
  • Abnormal  bleeding in the uterus
  • Abnormal thickening of the lining of the uterus (endometrial hyperplasia)
  • Cancer of the uterus (a three times higher risk than those without PCOS)

Other disorders:

  • Sleep apnoea. Sleep apnoea is more common in women who are overweight and have PCOS, and is associated with numerous negative health outcomes, including increased risk for heart disease.
  • Depression and anxiety. Hormonal changes and symptoms like unwanted hair growth can negatively affect emotions.

What is the link between weight gain, insulin resistance and PCOS?

Approximately 70% of women with PCOS are overweight or obese. Excess weight, especially central obesity, is strongly associated with insulin resistance and systemic inflammation, both contributing factors to PCOS and other health conditions. In teenagers, obesity is the highest cause of anovulation (not ovulating) that continues into adulthood.

During PCOS, the ovaries produce abnormally high levels of androgen (male) hormones. These control the development of male characteristics and prevent the ovaries from releasing eggs, and can trigger extra hair growth (hirsutism) and acne. High androgen levels also contribute to insulin resistance through causing weight gain, resulting in the same metabolic outcomes as MetS. At the same time, increasing insulin leads to further androgen production, preventing menstruation and ovulation. It is therefore thought that high androgen levels together with insulin resistance creates a snowball-effect where increased insulin leads to higher androgen levels, which in turn increases insulin resistance and worsens PCOS.

What is an ovarian cyst?

An ovarian cyst is any collection of fluid, surrounded by a thin wall, within an ovary. Small ovarian cysts, called follicles, are normal and occur in both ovaries. A follicle that is larger than about 2cm is termed an ‘ovarian cyst’.

The diagnosis of polycystic ovaries is made when there are either 12 or more ovarian cysts, or when one or both ovaries are bigger than 10cm3.

Although 20% of all women have ovarian cysts, it does not mean you necessarily have polycystic ovary syndrome or vice versa.  These cysts are only one of the components of PCOS.

What are the treatments for PCOS?

Due to PCOS being a complex disorder resulting from many different underlying factors, there are no pharmaceutical drugs specifically designed for the condition. Rather, medications and treatments are prescribed to address specific symptoms, such as high blood sugar or unwanted hair growth.

Principles of the treatment of PCOS

  • Treatment is focussed on symptoms
  • Patients with mild symptoms might only require lifestyle modification and supplements
  • Treatment should be chronic and adapted to the changing circumstances, personal needs and expectations of the patient

Drug-based treatments

Drugs that are used for PCOS and its treatment include:

  • Hormonal therapies, including combination birth control pills, progestin, clomid (an anti-oestrogen medication) and gonadotropins. These therapies can work to reduce androgen production, or stimulate ovulation and menstruation.
  • Metformin, used to improve the insulin related aspects of the condition
  • Topical drugs, like creams, which act to prevent hair growth, acne, etc.

Lifestyle modifications

Lifestyle modification should be recommended to every woman with PCOS or any of its symptoms. Maintenance of healthy habits might reduce insulin resistance and its consequences, restore ovulation and improve fertility. These include:

  • Maintaining a healthy weight. Weight loss can reduce insulin and androgen levels and may restore ovulation. Even slight reductions (as little as 5%) can make a difference and improve fertility.
  • Avoidance of processed, high-carbohydrate foods. Diet should be centred upon plant-based, minimally processed foods comprising complex carbohydrates, healthy fats and proteins.
  • Staying active. Exercise helps lower blood sugar levels, reduce inflammation and improve hormonal regulation.
  • Avoiding toxic substances, such as tobacco and alcohol. Not only can these cause direct damage via oxidative stress, but also affect hormonal regulation and inflammation.


Due to the complex nature of PCOS and MetS, many underlying deficiencies and imbalances develop and, in turn, contribute to these conditions getting worse. These are often in vitamins, minerals and compounds which the body naturally makes and uses, but due to metabolic imbalance, is making too little, getting rid of too much, or using incorrectly. For this reason, providing your body with these substances can prove highly beneficial to improving outcomes and symptoms of PCOS and MetS. Some of the most well-researched and effective supplements are:

  • Inositol, a naturally occurring nutrient which exist in the body in two forms: myo (MI) and D-chiro-inositol (DCI). Both act in fertility, reproduction and metabolic health. Problems in the balance between these two forms of inositol results in reduced insulin sensitivity and poor ovary function. Clinical studies have shown that inositol, especially at the ratio provided by OviVance, improves regulation of insulin and insulin sensitivity, ovulation and follicular maturation, egg quality and quantity and restores menstrual cycle regularity.
  • Vitamin D is well known to assist in MetS and PCOS through reduction in insulin resistance, dyslipidaemia and obesity.
  • Magnesium assists metabolic aspects of female health, especially in terms of MetS, PCOS and reducing the risk of gestational diabetes.
  • Selenium has well established roles in MetS and PCOS, insulin sensitization, and an inverse relationship with androgenic hormone levels
  • Zinc is important when addressing PCOS and MetS, especially through reducing inflammation and oxidative stress, improving insulin sensitivity, blood sugar regulation and dyslipidaemia.

OviVance, a unique blend of vitamins and minerals specially formulated by MNI to aid in improving fertility and PCOS, contains all of these vital substances in optimal amounts, helping you to enhance your reproductive and metabolic health as well as ovary function, whether you suffer from PCOS or just wish to improve your fertility. Try OviVance to take control of your reproductive health today.

  1. Hursting SD, PhD, MPH. Obesity, Energy Balance and Cancer: Trends, Targets and Transgenics. 2003. Department of Carcinogenesis, University of Texas
  2. Linkov F, PhD. Cancer Epidemiology: The Need for Global Information Sharing in obesity and cancer? World Congress of Epidemiology, Aug 2011
  3. Pazaitou-Panayiotou, K., Polyzos, S. A. and Mantzoros, C. S. (2013), Obesity and thyroid cancer: epidemiologic associations and underlying mechanisms. Obesity Reviews. doi: 10.1111/obr.12070
  4. Yehuda-Shnaidman E, Schwarts B. Mechanisms linking obesity, inflammation and altered metabolism to colon carcinogenesis. Obes Rev. 2012 Dec: 13(12): 1083-95. Epub 2012 Sep 3.
  5. Birk S, Peeters A, Mackholder K, O’Brien P, Brown W. A systemic review of the impact of weight loss on cancer incidence and mortality. Obesity Review, Vol 13, Issue 10, pgs. 868-891, Oct 2012
  6. Gallagher EJ, MB BCH BAO MRCPI, LeRoith D, MD, PhD. Epidemiology and molecular mechanisms tying obesity, diabetes and the metabolic syndrome with cancer. Diabetic Care, Vol36, Sup 2, Aug 2013
  7. Messiah SE, Lipschultz SE, Natale RA, Miller TL. The imperative to prevent and treat childhood obesity: why the world cannot afford to wait. Clinical Obesity
  8. The Cancer Association of South Africa.  Accessed 16 October 2013
  9. Krygsman, A. Can restriction of carbohydrate and/or omega fatty acids prevent breast cancer development? Dept. of Physiological Sciences, University of Stellenbosch.
  10. Albrecht, C MD. Cancer stakes its Territory- Causes and Link to Stress. Head of research, CANSA, Aug 2012
  11. Herbst MC, Prof. Fact sheet on Colorectal Cancer. Cancer Association of South Africa. June 2013
  12. Donna Kerrigan, M.S. Jeanne Kelly. Brian Hollen.  Understanding Cancer and Related Topics, Understanding Cancer Genomics. National Cancer Institute.
  13. Shmoop Editorial Team. “The Cell Cycle, Cellular Growth, and Cancer” Shmoop University, Inc., 11 Nov. 2008. Web. 17 Oct. 2013.
  14. Chow AY, PhD. (2010) Cell Cycle Control by Oncogenes and Tumour Suppressors: Driving the Transformation of Normal Cells into Cancerous Cells. Nature Education 3(9):7
  15. National Cancer Institute at the National Institutes of Health. Fact Sheet: Obesity and Cancer Risk.  Accessed 18 October 2013
  16. Nissen MJ, Shapiro A, Swenson KK. Changes in weight and body composition in women receiving chemotherapy for breast cancer. Clin Breast Cancer, 2011 Mar;11(1):52-60
  17. The Cancer Association of South Africa. Breast Cancer – Big & Small Let’s save them all. Accessed 16 October 2013
  18. National Academy of Sciences. The Role of Obesity in Cancer Survival and Recurrence: Workshop Summary 2012