Margarine is much worse than butter

In the 1970s, I was instructed to swap from butter to margarine. Fortunately, I did not like the taste of margarine and, over the years, the more research I conducted on the topic the more I realised that we were being lead astray and even lied to about this. Today, when I ask any of my audiences, sometimes in the hundreds, “Who thinks margarine is better for you than butter?” I rarely get a positive response. It seems most people already know that margarine is a dangerous substitute.

It appears that there is no scientific evidence that margarine is healthier than butter. In fact, evidence suggests the exact opposite is true. This is summed up first of all in one of my earlier articles that showed saturated fat is not the demon it is made out to be and may even be associated with reduced heart attack (another myth shattered). At least that is what the biggest and best studies show. Furthermore, we consume many more Omega 6 (vegetable) oils today than our ancestors did and this is having a negative impact on our health. These oils are not just in our margarine but also hidden in most of our food. We ate margarine for 50 years thinking it was made up of so-called “good fats” only to find out it was laden with the deadliest form of fat: trans fats. Finally, there is emerging evidence that margarine may not be good for our health, with or without trans fats, and is nowhere near a natural food; the push to sell more margarine has come from organisations like the Heart Foundations around the world and branches of margarine companies with strong vested interests in promoting margarine sales.

I think one of the best things to have happened to the Australian cuisine is Master Chef. It has inspired a whole generation to go back to the kitchen and start cooking again. It has also encouraged the increased use of butter over vegetable oils, something the Heart Foundation and the margarine manufacturers did not like so they had to come up with campaigns to sway people back to margarine. Interestingly one of the foundation’s ploys was to create, through a public relations company, a group called “Mums United” which pretends to be a grassroots mothers campaign against evil butter. According to David Gillespe (Sweet Poison) and the “duck test” of inductive reasoning, “It walks like a margarine advertisement and quacks like a margarine advertisement, so guess what it I think it is?” And the margarine companies fund it! Some of the group’s tactics have included offering financial support to people who pledged not to eat butter. So much for it being a grassroots organisation. It seems that margarine interests have taken some of the old tactics taught to us by the tobacco industry and big drug companies.

I want to make it very clear that I have no vested interests in anything other than people’s health and the truth.

Various heart associations around the world recommend increasing Omega 6 (vegetable) oil consumption and reducing saturated fats, based on flawed studies that have been seriously questioned due to data manipulation. This includes the omission of relevant trials with unfavourable outcomes—that is, leaving out any negative studies ^1,2,3 and including studies that combine both Omega 3 (fish oils, which are good for you) and Omega 6 consumption together under the title of “polyunsaturated fats.” The associations even included poorly done studies as long as the studies showed the desired results. This type of publication bias is well known in the research literature particularly with big drug companies trying to show that their drugs work better than they really do.

Margarine is far from being a natural product—well, as much as you can claim that plastic is natural. The major components of margarine are “vegetable” oils, obtained from foods such as sunflower seeds, rapeseed, or potentially genetically modified canola and soya beans. These oils are usually extracted using the application of pressure, heat and possibly solvents and then treated with sodium hydroxide to “neutralise” certain fats in the oil. It is then bleached, filtered and steam-treated to produce what is essentially a colourless, flavourless murky looking liquid. The liquid is converted into a solid at room temperature through esterifcation, which uses high temperature and pressure, along with enzymes or acids, to harden the oil—this is also called hydrogenation. Hydrogenation produces trans fats that are strongly linked with heart disease, cancer and other chronic illnesses. The final product is coloured and flavoured with various agents to make it feel and look like butter. Then finally ingredients like plant sterols and stanols and alpha linolenic acid is added to make it appear healthy. The finished product is not natural or healthy.

Plant stanols and sterols are added to reduce cholesterol. However, overwhelming evidence now shows cholesterol is just a poor indicator of heart attack, not the cause ⁴. It is just the warning sign or, if I can use an analogy, like a fire alarm in your home, it is not the problem itself, but a warning about the problem. You can get plenty of stanol and sterols in nuts, beans and seeds, which are not only natural but also full of other healthful benefits including vitamins, antioxidants, minerals and so much more and reduce all forms chronic illness. Margarine manufacturers can trumpet the presence of “heart-healthy” Omega 3 fats on the label, however they are putting plant-based Omega 3 fats (alpha linolenic acid) that do not act like Omega 3 from fish sources. They still have to be converted in our body to fish-like Omega 3s. It is also questionable whether they will be oxidised or not and therefore of any value. Adding a nutrient to toxic food does not make it healthy. Do you really believe the advertising?

Margarine is a major source of trans fatty acids, the intake of which has risen since the early 20th century. Trans fatty acids are synthetic fats produced as a byproduct of the hydrogenation of liquid vegetable oils, making them into solid margarine. An abundance of data indicates that consumption of trans fatty acids increases the risk of coronary heart disease (CHD), cancer, diabetes and other chronic illnesses. Margarine companies are now obliged to list the amount of trans fats on the side of the packet. Until recently however, margarine has been the single biggest source of these very toxic fats.

In a study of women, long-term margarine and trans fat consumption was associated with a 67% increased risk of heart disease ⁵. The decrease in intake of trans fatty acids in Denmark saw a 50% reduction in the number of deaths from ischemic heart disease ⁶. A recent study found that trans fatty acids promote cardiovascular disease by triggering inflammatory processes in the cells lining blood vessels ⁷. Increased intake of trans fatty acids has also been linked with an increase in the risk of colorectal tumours by about 86% ⁸. The potentially damaging effects of trans fats may also be passed from a mother to her child during breast feeding and can lead to an increase in cardiac insulin resistance when the kids become adults ⁹.

During the past 150 years, the Industrial Revolution and the emergence of agribusiness with processed foods, grain-fattened livestock, and hydrogenation of vegetable fats have considerably reduced the available content of Omega 3 fatty acids and increased that of Omega 6 fatty acids. While Omega 6 and 3 oils are considered essential fatty acids, the research is now showing that it is important to get the correct balance of the fats. An imbalance leads to various metabolic diseases. Western diets are now deficient in Omega 3 fatty acids and are laden with excessive amounts of Omega 6 fatty acids compared with the diet on which human beings evolved and their genetic patterns were established. Our diets now have 14 to 20 times more Omega 6 (vegetable oil) than Omega 3 fatty acids. This imbalance is now linked with diseases such as heart attack, stroke, cancer, obesity, insulin resistance, asthma, arthritis, depression, ADHD, Alzheimer’s disease and even premature ageing. The ideal balance is less than 4:1 or even 1:1 Omega 6 and 3, respectively.

Omega 6 oils such as corn, safflower, cottonseed, sunflower, and soya are now in nearly all our foods. Apart from the obvious consumption of vegetable oils and margarine you buy in the supermarket—which I hope you are now not going to buy—Omega 6 oils are hidden in most foods. You will find vegetable oils in just about every processed and semi-processed food including bread, cakes, and breakfast cereals and in lots of the plant-based drinks like almond or soya milk the main ingredient is often vegetable oil. All the takeaway foods, frozen and packaged dinners have Omega 6 oils. Even the “new” Mediterranean diet is laden with Omega 6 oils. When you buy olives, pesto sauce, sundried tomatoes or anything soaking in oil it is now vegetable oil in which it is soaked, not olive oil because vegetable oil is cheaper, unless you go to Italy where most foods are still soaked in olive oil. It is almost impossible to get away from the excess of Omega 6 oils. Time to read the labels! Factory produced eggs have 20 times more Omega 6 than Omega 3 compared to free-range eggs, which have a ratio of 1:1. Similarly, grain-fed beef (which I do not recommend you eat) has around 20:1 Omega 6 to Omega 3 oils because the cows are fed grains rich in Omega 6 oils. Alpha linolenic acid is found in the grass and is converted into the important Omega 3 oils by the animals. It is found only in grass-fed animals. Grass-fed cows are also a lot less stressed and have as a result lower levels of inflammation.

On the topic of animals fats, I have highlighted in earlier articles that despite claims by the Heart Foundation there is no scientific evidence to suggest that saturated fat through dairy consumption is associated with increased heart attack. By contrast, in a 16-year prospective study of 1,529 adult Australians, researchers found a possible beneficial association between intake of full-fat dairy and cardiovascular mortality ¹⁰. Whoops… the Heart Foundation got it wrong again.

By contrast, the Framingham study, which followed people for 20 years (a very long and comprehensive study) and recorded heart attack incidence, found margarine intake increased coronary heart disease in men ¹¹. The scientists in their very conservative language wrote, “These data offer modest support to the hypothesis that margarine intake increases the risk of coronary heart disease.” Not the opposite. In the second ten-year period of the study, the group eating the most margarine had 77% more heart attacks than the group eating none.

Studies that investigated increasing the amount of Omega 6 without a subsequent increase in animal-based Omega 3 (fish oil) consistently found an increase in coronary heart disease (CHD) and all-cause mortality. In an early study, published in 1965, researchers found that people consuming corn oil, a rich source of Omega 6, had a 4.64 times (over 400%) increased risk for both chronic heart disease and death from all causes ¹². In the conservative language of scientists, the authors of the study concluded that corn oil is “possibly harmful.” In another study, in which participants consumed more safflower oil and a safflower oil polyunsaturated margarine, participants had a 49% increased risk of death from all causes including a 91% increase from chronic heart disease and 96% from CVD ¹³.

In one study specifically on Omega 6 consumption in more than 9,000 people, the risk of non-fatal heart attack and death from coronary heart disease was significantly increased among women consuming the n-6 specific polyunsaturated fatty acid (PUFA) diet for one year or less ¹⁴. Women consuming this n-6 specific PUFA diet for any duration had non-significant trends to increased risk of non-fatal heart attack and coronary heart disease and any cardiovascular event including death and stroke ¹⁴. In fact the Lyon Diet Heart Study found that after follow up of 27 months, non-fatal heart attack and coronary heart disease death and overall mortality were 73% and 70% lower in the experimental group who consumed lower Omega 6 oils and replaced vegetable oils with olive oil. This study also demonstrated that lowering linoleic acid (Omega 6 vegetable oil) below 50% is not harmful and may even be beneficial, producing a profound risk reduction in coronary heart disease.

A recent meta-analysis of randomised controlled trials investigating polyunsaturated Omega 6 oil consumption (vegetable oils and margarine) found that there is absolutely no scientific justification for recommending the increased consumption of Omega 6 oils ². Or, to quote their conclusion, “Advice to specifically increase n-6 PUFA intake … is unlikely to provide the intended benefits, and may actually increase the risks of CHD and death.” The study found for non-fatal myocardial infarction (heart attack) and death from coronary heart disease there was an increased risk of 13% for diets with increased Omega 6. The studies that substituted Omega 6 for saturated fatty acids without simultaneously increasing Omega 3 oils also produced an increase in risk of death. It seems the vegetable oils are just as bad as the trans fats and what we are really lacking are the Omega 3 fish oils.

Arachidonic acid is produced in the body from too much Omega 6 and produces chemical messengers that lead to inflammation in the body called eicosanoids and cytokines. The increase in linoleic acid (Omega 6) has been shown to increase the oxidation of low-density lipoprotein (LDL cholesterol) ¹⁵. There is nothing wrong with cholesterol until it is oxidised. The evidence from animal studies also shows that a high linoleic acid diet can promote certain cancers ¹⁶ and other inflammatory diseases. In a study of 203,193 men and women, increased intakes of Omega 6 fatty acid (linoleic acid) doubled the risk of ulcerative colitis, an inflammatory bowel disease, which has seen a rapid increase during recent decades. By contrast the highest intakes of Omega 3 were associated with 77% reduction in the risk of the disease ¹⁷. Omega 6 fatty acids are present in the cell membrane of colon cells in the form of arachidonic acid. This can be metabolised to chemical messengers in the body called prostaglandin E2, leukotriene B4 and thromboxane A2, all of which are associated with inflammation. On the other hand, Omega 3 fatty acids, including docosahexaenoic acid (DHA) may prevent colonic inflammation.

There is also research showing that too much Omega 6 oil is contributing to premature ageing. Telomeres, which are in all our cells, are thought to be markers of our ageing because they reflect cumulative oxidative stress and inflammation. The shorter they are, the more we have aged. Because the metabolites of Omega 6 promote inflammation, it is believed that an increase in Omega 6 fatty acid content in our diet decreases the leukocyte telomere length ^18,19 and hence speeds up the ageing process.

It is time to rethink our fat consumption. The research shows that fat in itself is not bad—in fact, it is essential and the move away from fat has lead to a more obese and sicker population. What we need to do however is decrease our consumption of processed oils like margarine and vegetable oils and increase our Omega 3 fish oils along with Omega 9 oils, including olive oil.

References

1.     Ramsden 2009;

2.     Ramsden et al. 2010,

3.     Ramsden et al. 2011

4.     Dingle 2011 The Great Cholesterol Deception

5.     Willett et al. 1993

6.     Stender and Dyerberg 2004

7.     Harvey et al 2008

8.     Vinikoor et al. 2010

9.     Osso et al. 2008

10. Bonthuis et al. 2010

11. Gillman 1997

12. Rose et al. 1965

13. Woodhill et al. 1978

14. Frantz et al. 1989

15. Tsimikas et al. 1999

16. Welsh 1992

17. Hart 2008

18. Kang 2010;

19. Kiecolt-Glaser 2012

Epigenetics and Disease

Various genetic messages are “turned on” (expressed) or “turned off” (silenced) through epigenetic processes like DNA methylation. When turned off, it is as if a protein glove covers the DNA message so it can no longer be read or acted upon. Although epigenetic modification of our genes is a natural part of our development and well being, these processes can interact with various chemicals in our environment and in foods and drinks we consume, leading to the development of disease. Conversely, epigenetic actions of other compounds in our environment and nutrition are thought to hold the key to providing therapies to fight and prevent disease.

If a genetic mutation for a disease is “turned off” by epigenetic markers, that particular gene—in such an instance—cannot cause disease. For example, an individual may have inherited the genes for a particular disease; if, however, those genes are not expressed, the disease will not develop. However, change to the epigenetic markers (of a mutated gene) could cause the mutated gene to “tune into” and hence develop a specific disease.

Many human diseases have been associated with epigenetic modifications due to environmental exposure. These include cancer, obesity, diabetes, asthma, multiple sclerosis, mental illness and behavioural disorders as well as premature ageing ^1,2,3,4.

Humans are most vulnerable to epigenetic changes during the development of the embryo in the womb, embryogenesis, where epigenetic disruptions can be passed down through multiple generations ⁵. One study on diethylstilbestrol (DES), an environmental oestrogen, found that DES induced a genetic predisposition to a certain cancer and congenital birth defects that was passed down two generations ⁶. Similarly, foetal exposures to plasticizers such as bisphenol A, a chemical found commonly in plastic, contribute to epigenetic changes, which lead to immune abnormalities. Maternal smoking leads to increased pulmonary disease in adulthood including asthma; and certain therapeutic drug exposure leads to vascular defects. These can all be classified as epigenetic changes.

During the past decade, evidence has accumulated showing that apart from genetic alterations (mutations), epigenetic alterations play a major role in the initiation and progression of cancer ⁷. Human cancers arise from a multi- step process characterised by tumour initiation and progression ⁸ but only five percent of cancers can be attributed to heredity. Genetics alone cannot explain all of the properties of cancer. It is now understood that epigenetic abnormalities and the turning off and on of certain genes play a major role in tumour genesis—the development of and proliferation of tumours ^9,10.

Cancer, which is caused by uncontrolled cellular growth, is induced by mutations in the DNA, which can be initiated by errors in the DNA or foreign chemicals called carcinogens. In addition to uncontrolled cellular growth, a characteristic of cancer is inhibition of normal programmed cellular death, called apoptosis. When the body’s DNA makes mistakes in a cell, the mistakes are either fixed by additional DNA repair mechanisms or the cell is destroyed to prevent further damage (apoptosis). Unfortunately, the genes that are responsible for destroying rogue cells can be silenced (turned off) through epigenetics and, as a result, mistakes in the DNA cannot be rectified before they spread. The genes associated with cellular pathways that are prone to cause cancer are called oncogenes. The silencing of tumour‑suppressing genes, activation of oncogenes, and defects in DNA can be caused by epigenetic mechanisms, which can affect several if not many of the steps in a cancer line ¹¹.

We have literally removed the various roadblocks to formation of cancer. Many of the genes that are inactivated by methylation in carcinogenesis have classic tumour‑suppressor functions or play a critical role in cell cycle control (repair of damage to DNA) apoptosis, differentiation, angiogenesis, metastasis, growth factor response, drug resistance and detoxification ¹². An incorrect change in the methylation of the DNA caused by epigenetic carcinogens is the most common activation of cancer cell lines. Although methylation changes occur to different genes depending on the type of cancer, all cancers undergo changes in methylation, suggesting DNA methylation is a major factor in tumour development and can be used as a genetic marker in tumour development ¹³.

To put this in perspective, methylation in some areas of the DNA, called CpG sites, in some tumour suppressor coding regions contributes to as much as 50% of all inactivating mutations in some cancers and 25% of cancers in general.

In contrast to genetic changes in cancer, epigenetic changes are gradual in onset and are progressive. Their effects are dose-dependent and are potentially reversible which increases the scope for the development of epigenetic therapies for disease ¹⁴. These observations present new opportunities in cancer risk modification and prevention using dietary and lifestyle factors as well as treatment as you will see below. In this regard, folate, a water-soluble B vitamin, has been a focus of intense interest because of an inverse association between folate levels and the risk of several malignancies (in particular, colorectal cancer) and because of its potential ability to modulate DNA methylation. Through this process of supplementing with folate, scientists have achieved a certain degree of reprogramming even in adult cell DNA. The use of such inhibitors as folate has been shown to reactivate expression of tumour‑suppressor genes that would otherwise be silenced and a cancer would develop. Treatment for myelodysplastic syndrome, a form of leukaemia, with epigenetic therapies is already approved for use in the U.S. and there are a host of other treatments that continue to show promise ¹⁵.

Even more promising are the roles of diet and lifestyle. In a study of 30 men with low-risk prostate cancer who decided against conventional medical treatment such as surgery, radiation, chemotherapy or hormone therapy, three months of major lifestyle changes significantly lowered the level of prostate cancer. The changes included eating a diet rich in fruits, vegetables, whole grains and legumes and incorporating moderate exercise such as walking each day along with an hour of daily stress management ¹⁶.

Six of the control patients in this study underwent conventional treatment due to an increase in prostate specific antigen (PSA) levels or progression of disease measured by magnetic resonance imaging (MRI) during the 3 months, while none of the lifestyle group did.  PSA levels decreased four percent in the experimental lifestyle group but increased by six percent in the control (no change in lifestyle) group. Other markers such as the growth of prostate cancer cells (LNCaP) were inhibited almost eight times more in blood serum from the experimental group than blood serum from the control group (70% versus nine percent). However, even more definitively, the changes in serum PSA and in prostate cancer cell growth (LNCaP) were positively associated with the degree of change in diet and lifestyle. That is, the more lifestyle changes the men made, the greater the reduction in the prostate cancer markers. The lifestyle group were literally reversing their cancer.

The researchers found even more profound changes when they compared DNA from prostate biopsies taken before and after the lifestyle changes. After only three months, the men had changes in expression of about 500 genes, including 48 that were turned on and 453 genes that were turned off. The activity of disease-preventing genes increased while a number of disease-promoting genes, including those involved in prostate cancer and breast cancer, shut down. The lead researcher, Professor Dean Ornish, noted, “The implications of our study are not limited to men with prostate cancer” ¹⁶. In addition to the benefits in prostate diagnosis the men lost weight, lowered their blood pressure and risk of heart attack and stroke and saw other health improvements while reporting no negative side effects.

There is currently a great deal of interest in the promising chemo-preventive actions of polyphenols, large organic molecules, such as curcumin from curry, resveratrol found in grapes and berries and especially Epigallocatechin-3-Gallate (EGCG) the major polyphenol in green tea ¹⁷. EGCG in green tea has the ability to affect DNA epigenetics to fight cancer beyond just its antioxidant potential. For example, treatment of human oesophageal cancer cells with EGCG caused tumour suppressor genes, the genes that stop cancers from growing, to be “turned on.” The activity of EGCG has also been shown to possibly act to reduce cancer activity in prostate cancer cells ¹⁷.

Other studies link obesity and malnutrition (low nutrient-dense foods) in parents to hypertension in offspring and disease risk in offspring later in life ¹⁸, specifically with regard to obesity and the onset of diabetes later in life ¹⁹. Low-weight newborn babies are biologically different than their bigger counterparts. Smaller infants have fewer kidney nephrons, altered metabolism and are more insulin-resistant. These differences show how dietary habits of the mother during pregnancy can alter the expression of the genes of their offspring in such a way that they will respond differently to the environment that follows after birth. Placental and foetal growth is at its most vulnerable to maternal nutrition status in the first trimester of pregnancy. Promotion of a healthy, nutritionally balanced womb environment will not only ensure optimal foetal development but also reduce the risk of chronic disease in adulthood ²⁰. In support of this, it has been found that folate levels in pregnant women affect DNA methylation in a number of different gene promoter areas associated with infant health.

Some of the most well known studies linking epigenetics and obesity have involved “agouti” mice. Over the past twenty years there have been numerous studies indicating that impaired embryonic, foetal or infant nutrition as a result of out processed western diet and environments can lead to greater risk of obesity and metabolic compromise in later years ²¹. For example, a short‑term dietary intervention in pregnant agouti mice, in the form of supplements of folic acid, vitamin B 12, choline and betaine, have shown long‑lasting beneficial influences on the health and appearance of the offspring for multiple generations ²². By contrast, selectively bred diet‑induced obesity dams (mothers) that were made obese during gestation and lactation had more obese, insulin-resistant children who developed abnormalities of brain neurotransmitter metabolism compared with offspring of lean diet‑induced obesity dams or dams that were diet‑resistant ²³. That is why there is so much emphasis now on pregnant mothers supplementing, particularly with B vitamins. In a study of sheep, metabolic and hormonal signals before birth increased the expression of genes that regulate fat and the conversion of simple sugars into fatty acids in the fat around the kidneys of sheep ²⁴.

In one study, two types of rats were bred: one to develop diet‑induced obesity and the other that was prone to be diet‑resistant. Researchers found that the diet‑induced obesity rats would defend their increased body weight when fed a high-fat diet (31%) whereas the diet‑resistant rats would adjust their (high-fat) diet accordingly to maintain their lean physique. The study also found that the diet‑induced obesity rats, even after long periods of calorie restriction, would return to their higher weight once food was available freely, even when on a five percent fat diet ²⁵.

In other studies, researchers found that in a population with a genetic predisposition toward obesity, the effects of maternal obesity accumulated over successive generations to shift the population distribution toward an increased adult body weight. Perhaps this is something we are heading toward now in the human population…?

It is clear that epigenetic mechanisms may also drive psychiatric and mental disorders. In particular what your mother eats during pregnancy and you eat during childhood not only may influence your adult brain function and its eventual decline as you age, but also may influence your children’s cognitive potential and mental health ²⁶. A foetus that endures poor nutrition during gestation spares the growth of vital organs such as the brain at the expense of tissues such as muscle; the pancreas adapts its metabolism to the limited nutrition ²⁷. Following on from this, increasing evidence indicates that a disturbance in early neurodevelopment may lead to a vulnerability to schizophrenia in adolescence or adulthood ²⁸.

Twin studies have shown that people with schizophrenia and bipolar disorder have changes in genetic activity caused by their respective environments. The findings provide the strongest evidence yet that such gene changes might cause these conditions. A study that scanned the genome of 22 pairs of identical twins (one twin in each pair was diagnosed with schizophrenia or bipolar disorder) found, as expected, that the twins had identical DNA. However, they showed significant differences in epigenetic markings and these changes were on genes that have been linked with bipolar disorder and schizophrenia ²⁹.

Regardless of which condition the twin had, the most significant differences, with variations of up to 20% in the amount of methylation, were in the promoter “switch” for a gene called ST6GALNAC1, which has been linked with schizophrenia. The scans also revealed methylation differences in Gpr24, a gene previously linked to bipolar disorder ²⁹. In support of this, other studies have found differences of up to 25% in methylation of the same gene compared with controls.

Growing evidence suggests how we age is very much epigenetic-related. Some of the strongest, decade-old evidence shows progressive changes in DNA methylation in tissues in the ageing colon, stomach, oesophagus, liver, kidney and bladder adding increased importance to the role of diet and lifestyle in how we age.

Despite the role of our parents’ diet and lifestyles on our future and the future of our own offspring, research shows we can change this outcome by nutrition and lifestyle changes. We are largely in control of our own destiny. From epigenetics, we are learning that it is not all in the genes.

References

1.     Bollatti and Baccarelli 2010;

2.     Dolinoy et al. 2007;

3.     Isles and Wilkinson 2008;

4.     Weidmann et al. 2007

5.     Attig et al. 2010

6.     Newbol 2004

7.     Nystrom and Mutanen 2009

8.     Dworkin, Huang and Toland 2009

9.     Esteller 2008;

10.  Shikhar, Kelly and Jones 2010

11.  Herceg 2007

12.  Kim 2006

13.  Banerjee 2009

14.  Adcock et al. 2006

15.  Issa 2006

16.  Ornish et al. 2008

17.  Link, Balaguer and Goel 2010

18.  Friaz et al. 2011

19.  Ryan 2011

20.  Wu et al. 2004

21.  Gluekman and Hanson 2008

22.  Freeman 2009

23.  Levin et al. 2005

24.  Muhlhausler et al. 2007

25.  Levin 2008

26.  Williams 2008

27.  Jones PB, Rantakallio P, Hartikainen AL, Isohanni M, Sipila P

28.  Brown and Susser 2008

29.  Dempster, Pidsley et al 2011