Cardiovascular disease

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https://en.wikipedia.org/wiki/Cardiovascular_disease

Cardiovascular disease
Micrograph of a heart with fibrosis (yellow) and amyloidosis (brown). Movat's stain.
Specialty	Cardiology
Symptoms	Chest pain, shortness of breath, fatigue, loss of consciousness
Complications	Heart failure, heart attack, stroke, aneurysm, peripheral artery disease, sudden cardiac arrest.
Usual onset	Older adults
Types	Coronary artery diseases, stroke, heart failure, hypertensive heart disease, rheumatic heart disease, cardiomyopathy, Arrhythmia
Risk factors	Diabetes, high blood lipids, excess weight, Smoking, excessive drug use, and excessive alcohol intake
Prevention	Healthy eating, exercise, avoiding tobacco smoke, limited alcohol intake, Overall lifestyle changes
Treatment	Treating high blood pressure, high blood lipids, diabetes
Medication	Aspirin, beta blockers, blood thinners
Deaths	17.9 million / 32% (2015)

Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases (e.g. angina, heart attack), heart failure, hypertensive heart disease, rheumatic heart disease, cardiomyopathy, arrhythmia, congenital heart disease, valvular heart disease, carditis, aortic aneurysms, peripheral artery disease, thromboembolic disease, and venous thrombosis.

The underlying mechanisms vary depending on the disease. It is estimated that dietary risk factors are associated with 53% of CVD deaths. Coronary artery disease, stroke, and peripheral artery disease involve atherosclerosis. This may be caused by high blood pressure, smoking, diabetes mellitus, lack of exercise, obesity, high blood cholesterol, poor diet, excessive alcohol consumption, and poor sleep, among other things. High blood pressure is estimated to account for approximately 13% of CVD deaths, while tobacco accounts for 9%, diabetes 6%, lack of exercise 6%, and obesity 5%. Rheumatic heart disease may follow untreated strep throat.

It is estimated that up to 90% of CVD may be preventable. Prevention of CVD involves improving risk factors through: healthy eating, exercise, avoidance of tobacco smoke and limiting alcohol intake. Treating risk factors, such as high blood pressure, blood lipids and diabetes is also beneficial. Treating people who have strep throat with antibiotics can decrease the risk of rheumatic heart disease. The use of aspirin in people who are otherwise healthy is of unclear benefit.

Cardiovascular diseases are the leading cause of death worldwide except Africa. Together CVD resulted in 17.9 million deaths (32.1%) in 2015, up from 12.3 million (25.8%) in 1990. Deaths, at a given age, from CVD are more common and have been increasing in much of the developing world, while rates have declined in most of the developed world since the 1970s. Coronary artery disease and stroke account for 80% of CVD deaths in males and 75% of CVD deaths in females. Most cardiovascular disease affects older adults. In the United States 11% of people between 20 and 40 have CVD, while 37% between 40 and 60, 71% of people between 60 and 80, and 85% of people over 80 have CVD. The average age of death from coronary artery disease in the developed world is around 80, while it is around 68 in the developing world. CVD is typically diagnosed seven to ten years earlier in men than in women.

Types

Disability-adjusted life year for inflammatory heart diseases per 100,000 inhabitants in 2004

  No data

  Less than 70

  70–140

  140–210

  210–280

  280–350

  350–420

  420–490

  490–560

  560–630

  630–700

  700–770

  More than 770

There are many cardiovascular diseases involving the blood vessels. They are known as vascular diseases.

• Coronary artery disease (coronary heart disease or ischemic heart disease)
• Peripheral arterial disease – a disease of blood vessels that supply blood to the arms and legs
• Cerebrovascular disease – a disease of blood vessels that supply blood to the brain (includes stroke)
• Renal artery stenosis
• Aortic aneurysm

There are also many cardiovascular diseases that involve the heart.

• Cardiomyopathy – diseases of cardiac muscle
• Hypertensive heart disease – diseases of the heart secondary to high blood pressure or hypertension
• Heart failure – a clinical syndrome caused by the inability of the heart to supply sufficient blood to the tissues to meet their metabolic requirements
• Pulmonary heart disease – a failure at the right side of the heart with respiratory system involvement
• Cardiac dysrhythmias – abnormalities of heart rhythm
• Inflammatory heart diseases
  • Endocarditis – inflammation of the inner layer of the heart, the endocardium. The structures most commonly involved are the heart valves.
  • Inflammatory cardiomegaly
  • Myocarditis – inflammation of the myocardium, the muscular part of the heart, caused most often by viral infection and less often by bacterial infections, certain medications, toxins, and autoimmune disorders. It is characterized in part by infiltration of the heart by lymphocyte and monocyte types of white blood cells.
  • Eosinophilic myocarditis – inflammation of the myocardium caused by pathologically activated eosinophilic white blood cells. This disorder differs from myocarditis in its causes and treatments.
• Valvular heart disease
• Congenital heart disease – heart structure malformations existing at birth
• Rheumatic heart disease – heart muscles and valves damage due to rheumatic fever caused by Streptococcus pyogenes a group A streptococcal infection.

Risk factors

There are many risk factors for heart diseases: age, sex, tobacco use, physical inactivity, non-alcoholic fatty liver disease, excessive alcohol consumption, unhealthy diet, obesity, genetic predisposition and family history of cardiovascular disease, raised blood pressure (hypertension), raised blood sugar (diabetes mellitus), raised blood cholesterol (hyperlipidemia), undiagnosed celiac disease, psychosocial factors, poverty and low educational status, air pollution, and poor sleep. While the individual contribution of each risk factor varies between different communities or ethnic groups the overall contribution of these risk factors is very consistent. Some of these risk factors, such as age, sex or family history/genetic predisposition, are immutable; however, many important cardiovascular risk factors are modifiable by lifestyle change, social change, drug treatment (for example prevention of hypertension, hyperlipidemia, and diabetes). People with obesity are at increased risk of atherosclerosis of the coronary arteries.

Genetics

Cardiovascular disease in a person's parents increases their risk by ~3 fold, and genetics is an important risk factor for cardiovascular diseases. Genetic cardiovascular disease can occur either as a consequence of single variant (Mendelian) or polygenic influences. There are more than 40 inherited cardiovascular disease that can be traced to a single disease-causing DNA variant, although these conditions are rare. Most common cardiovascular diseases are non-Mendelian and are thought to be due to hundreds or thousands of genetic variants (known as single nucleotide polymorphisms), each associated with a small effect.

Age

Calcified heart of an older woman with cardiomegaly

Age is the most important risk factor in developing cardiovascular or heart diseases, with approximately a tripling of risk with each decade of life. Coronary fatty streaks can begin to form in adolescence. It is estimated that 82 percent of people who die of coronary heart disease are 65 and older. Simultaneously, the risk of stroke doubles every decade after age 55.

Multiple explanations are proposed to explain why age increases the risk of cardiovascular/heart diseases. One of them relates to serum cholesterol level. In most populations, the serum total cholesterol level increases as age increases. In men, this increase levels off around age 45 to 50 years. In women, the increase continues sharply until age 60 to 65 years.

Aging is also associated with changes in the mechanical and structural properties of the vascular wall, which leads to the loss of arterial elasticity and reduced arterial compliance and may subsequently lead to coronary artery disease.

Sex

See also: Cardiovascular disease in women

Men are at greater risk of heart disease than pre-menopausal women. Once past menopause, it has been argued that a woman's risk is similar to a man's although more recent data from the WHO and UN disputes this. If a female has diabetes, she is more likely to develop heart disease than a male with diabetes. Women who have high blood pressure and had complications in their pregnancy have three times the risk of developing cardiovascular disease compared to women with normal blood pressure who had no complications in pregnancy.

Coronary heart diseases are 2 to 5 times more common among middle-aged men than women. In a study done by the World Health Organization, sex contributes to approximately 40% of the variation in sex ratios of coronary heart disease mortality. Another study reports similar results finding that sex differences explains nearly half the risk associated with cardiovascular diseases One of the proposed explanations for sex differences in cardiovascular diseases is hormonal difference. Among women, estrogen is the predominant sex hormone. Estrogen may have protective effects on glucose metabolism and hemostatic system, and may have direct effect in improving endothelial cell function. The production of estrogen decreases after menopause, and this may change the female lipid metabolism toward a more atherogenic form by decreasing the HDL cholesterol level while increasing LDL and total cholesterol levels.

Among men and women, there are differences in body weight, height, body fat distribution, heart rate, stroke volume, and arterial compliance. In the very elderly, age-related large artery pulsatility and stiffness are more pronounced among women than men. This may be caused by the women's smaller body size and arterial dimensions which are independent of menopause.

Tobacco

Cigarettes are the major form of smoked tobacco. Risks to health from tobacco use result not only from direct consumption of tobacco, but also from exposure to second-hand smoke. Approximately 10% of cardiovascular disease is attributed to smoking; however, people who quit smoking by age 30 have almost as low a risk of death as never smokers.

Physical inactivity

Further information: Sedentary lifestyle

Insufficient physical activity (defined as less than 5 x 30 minutes of moderate activity per week, or less than 3 x 20 minutes of vigorous activity per week) is currently the fourth leading risk factor for mortality worldwide. In 2008, 31.3% of adults aged 15 or older (28.2% men and 34.4% women) were insufficiently physically active. The risk of ischemic heart disease and diabetes mellitus is reduced by almost a third in adults who participate in 150 minutes of moderate physical activity each week (or equivalent). In addition, physical activity assists weight loss and improves blood glucose control, blood pressure, lipid profile and insulin sensitivity. These effects may, at least in part, explain its cardiovascular benefits.

Diet

Further information: Saturated fat § Cardiovascular disease, Salt and cardiovascular disease, and Lipid hypothesis

High dietary intakes of saturated fat, trans-fats and salt, and low intake of fruits, vegetables and fish are linked to cardiovascular risk, although whether all these associations indicate causes is disputed. The World Health Organization attributes approximately 1.7 million deaths worldwide to low fruit and vegetable consumption. Frequent consumption of high-energy foods, such as processed foods that are high in fats and sugars, promotes obesity and may increase cardiovascular risk. The amount of dietary salt consumed may also be an important determinant of blood pressure levels and overall cardiovascular risk. There is moderate quality evidence that reducing saturated fat intake for at least two years reduces the risk of cardiovascular disease. High trans-fat intake has adverse effects on blood lipids and circulating inflammatory markers, and elimination of trans-fat from diets has been widely advocated. In 2018 the World Health Organization estimated that trans fats were the cause of more than half a million deaths per year. There is evidence that higher consumption of sugar is associated with higher blood pressure and unfavorable blood lipids, and sugar intake also increases the risk of diabetes mellitus. High consumption of processed meats is associated with an increased risk of cardiovascular disease, possibly in part due to increased dietary salt intake.

Alcohol

Further information: Alcohol and cardiovascular disease

The relationship between alcohol consumption and cardiovascular disease is complex, and may depend on the amount of alcohol consumed. There is a direct relationship between high levels of drinking alcohol and cardiovascular disease. Drinking at low levels without episodes of heavy drinking may be associated with a reduced risk of cardiovascular disease, but there is evidence that associations between moderate alcohol consumption and protection from stroke are non-causal. At the population level, the health risks of drinking alcohol exceed any potential benefits.

Celiac disease

Untreated celiac disease can cause the development of many types of cardiovascular diseases, most of which improve or resolve with a gluten-free diet and intestinal healing. However, delays in recognition and diagnosis of celiac disease can cause irreversible heart damage.

Sleep

A lack of good sleep, in amount or quality, is documented as increasing cardiovascular risk in both adults and teens. Recommendations suggest that Infants typically need 12 or more hours of sleep per day, adolescent at least eight or nine hours, and adults seven or eight. About one-third of adult Americans get less than the recommended seven hours of sleep per night, and in a study of teenagers, just 2.2 percent of those studied got enough sleep, many of whom did not get good quality sleep. Studies have shown that short sleepers getting less than seven hours sleep per night have a 10 percent to 30 percent higher risk of cardiovascular disease.

Sleep disorders such as sleep-disordered breathing and insomnia, are also associated with a higher cardiometabolic risk. An estimated 50 to 70 million Americans have insomnia, sleep apnea or other chronic sleep disorders.

In addition, sleep research displays differences in race and class. Short sleep and poor sleep tend to be more frequently reported in ethnic minorities than in whites. African-Americans report experiencing short durations of sleep five times more often than whites, possibly as a result of social and environmental factors. Black children and children living in disadvantaged neighborhoods have much higher rates of sleep apnea.

Socioeconomic disadvantage

Cardiovascular disease has a greater impact on low- and middle-income countries compared to those with higher income. Although data on the social patterns of cardiovascular disease in low- and middle-income countries is limited, reports from high-income countries consistently demonstrate that low educational status or income are associated with a greater risk of cardiovascular disease. Policies that have resulted in increased socio-economic inequalities have been associated with greater subsequent socio-economic differences in cardiovascular disease implying a cause and effect relationship. Psychosocial factors, environmental exposures, health behaviours, and health-care access and quality contribute to socio-economic differentials in cardiovascular disease. The Commission on Social Determinants of Health recommended that more equal distributions of power, wealth, education, housing, environmental factors, nutrition, and health care were needed to address inequalities in cardiovascular disease and non-communicable diseases.

Air pollution

Particulate matter has been studied for its short- and long-term exposure effects on cardiovascular disease. Currently, airborne particles under 2.5 micrometers in diameter (PM_2.5) are the major focus, in which gradients are used to determine CVD risk. Overall, long-term PM exposure increased rate of atherosclerosis and inflammation. In regards to short-term exposure (2 hours), every 25 μg/m³ of PM_2.5 resulted in a 48% increase of CVD mortality risk. In addition, after only 5 days of exposure, a rise in systolic (2.8 mmHg) and diastolic (2.7 mmHg) blood pressure occurred for every 10.5 μg/m³ of PM_2.5. Other research has implicated PM_2.5 in irregular heart rhythm, reduced heart rate variability (decreased vagal tone), and most notably heart failure. PM_2.5 is also linked to carotid artery thickening and increased risk of acute myocardial infarction.

Cardiovascular risk assessment

Existing cardiovascular disease or a previous cardiovascular event, such as a heart attack or stroke, is the strongest predictor of a future cardiovascular event. Age, sex, smoking, blood pressure, blood lipids and diabetes are important predictors of future cardiovascular disease in people who are not known to have cardiovascular disease. These measures, and sometimes others, may be combined into composite risk scores to estimate an individual's future risk of cardiovascular disease. Numerous risk scores exist although their respective merits are debated. Other diagnostic tests and biomarkers remain under evaluation but currently these lack clear-cut evidence to support their routine use. They include family history, coronary artery calcification score, high sensitivity C-reactive protein (hs-CRP), ankle–brachial pressure index, lipoprotein subclasses and particle concentration, lipoprotein(a), apolipoproteins A-I and B, fibrinogen, white blood cell count, homocysteine, N-terminal pro B-type natriuretic peptide (NT-proBNP), and markers of kidney function.^[63][64] High blood phosphorus is also linked to an increased risk.

Depression and traumatic stress

There is evidence that mental health problems, in particular depression and traumatic stress, is linked to cardiovascular diseases. Whereas mental health problems are known to be associated with risk factors for cardiovascular diseases such as smoking, poor diet, and a sedentary lifestyle, these factors alone do not explain the increased risk of cardiovascular diseases seen in depression, stress, and anxiety. Moreover, posttraumatic stress disorder is independently associated with increased risk for incident coronary heart disease, even after adjusting for depression and other covariates.

Occupational exposure

Main article: Occupational cardiovascular disease

Little is known about the relationship between work and cardiovascular disease, but links have been established between certain toxins, extreme heat and cold, exposure to tobacco smoke, and mental health concerns such as stress and depression.

Non-chemical risk factors

A 2015 SBU-report looking at non-chemical factors found an association for those:

• with mentally stressful work with a lack of control over their working situation — with an effort-reward imbalance
• who experience low social support at work; who experience injustice or experience insufficient opportunities for personal development; or those who experience job insecurity
• those who work night schedules; or have long working weeks
• those who are exposed to noise

Specifically the risk of stroke was also increased by exposure to ionizing radiation. Hypertension develops more often in those who experience job strain and who have shift-work. Differences between women and men in risk are small, however men risk having and dying of heart attacks or stroke twice as often as women during working life.

Chemical risk factors

A 2017 SBU report found evidence that workplace exposure to silica dust, engine exhaust or welding fumes is associated with heart disease. Associations also exist for exposure to arsenic, benzopyrenes, lead, dynamite, carbon disulphide, carbon monoxide, metalworking fluids and occupational exposure to tobacco smoke. Working with the electrolytic production of aluminium or the production of paper when the sulphate pulping process is used is associated with heart disease. An association was also found between heart disease and exposure to compounds which are no longer permitted in certain work environments, such as phenoxy acids containing TCDD(dioxin) or asbestos.

Workplace exposure to silica dust or asbestos is also associated with pulmonary heart disease. There is evidence that workplace exposure to lead, carbon disulphide, phenoxyacids containing TCDD, as well as working in an environment where aluminum is being electrolytically produced, is associated with stroke.

Somatic mutations

As of 2017, evidence suggests that certain leukemia-associated mutations in blood cells may also lead to increased risk of cardiovascular disease. Several large-scale research projects looking at human genetic data have found a robust link between the presence of these mutations, a condition known as clonal hematopoiesis, and cardiovascular disease-related incidents and mortality.

Radiation therapy

Radiation treatments (RT) for cancer can increase the risk of heart disease and death, as observed in breast cancer therapy. Therapeutic radiation increases the risk of a subsequent heart attack or stroke by 1.5 to 4 times; the increase depends on the dose strength, volume, and location. Use of concomitant chemotherapy, e.g. anthracyclines, is an aggravating risk factor. The occurrence rate of RT induced cardiovascular disease is estimated between 10% and 30%.

Side-effects from radiation therapy for cardiovascular diseases have been termed radiation-induced heart disease or radiation-induced cardiovascular disease. Symptoms are dose-dependent and include cardiomyopathy, myocardial fibrosis, valvular heart disease, coronary artery disease, heart arrhythmia and peripheral artery disease. Radiation-induced fibrosis, vascular cell damage and oxidative stress can lead to these and other late side-effect symptoms.

Pathophysiology

Density-Dependent Colour Scanning Electron Micrograph SEM (DDC-SEM) of cardiovascular calcification, showing in orange calcium phosphate spherical particles (denser material) and, in green, the extracellular matrix (less dense material)

Population-based studies show that atherosclerosis, the major precursor of cardiovascular disease, begins in childhood. The Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study demonstrated that intimal lesions appear in all the aortas and more than half of the right coronary arteries of youths aged 7–9 years.

Obesity and diabetes mellitus are linked to cardiovascular disease, as are a history of chronic kidney disease and hypercholesterolaemia. In fact, cardiovascular disease is the most life-threatening of the diabetic complications and diabetics are two- to four-fold more likely to die of cardiovascular-related causes than nondiabetics.

Screening

Screening ECGs (either at rest or with exercise) are not recommended in those without symptoms who are at low risk. This includes those who are young without risk factors. In those at higher risk the evidence for screening with ECGs is inconclusive. Additionally echocardiography, myocardial perfusion imaging, and cardiac stress testing is not recommended in those at low risk who do not have symptoms. Some biomarkers may add to conventional cardiovascular risk factors in predicting the risk of future cardiovascular disease; however, the value of some biomarkers is questionable. Ankle-brachial index (ABI), high-sensitivity C-reactive protein (hsCRP), and coronary artery calcium, are also of unclear benefit in those without symptoms as of 2018.

The NIH recommends lipid testing in children beginning at the age of 2 if there is a family history of heart disease or lipid problems. It is hoped that early testing will improve lifestyle factors in those at risk such as diet and exercise.

Screening and selection for primary prevention interventions has traditionally been done through absolute risk using a variety of scores (ex. Framingham or Reynolds risk scores). This stratification has separated people who receive the lifestyle interventions (generally lower and intermediate risk) from the medication (higher risk). The number and variety of risk scores available for use has multiplied, but their efficacy according to a 2016 review was unclear due to lack of external validation or impact analysis. Risk stratification models often lack sensitivity for population groups and do not account for the large number of negative events among the intermediate and low risk groups. As a result, future preventative screening appears to shift toward applying prevention according to randomized trial results of each intervention rather than large-scale risk assessment.

Prevention

Up to 90% of cardiovascular disease may be preventable if established risk factors are avoided. Currently practised measures to prevent cardiovascular disease include:

• Maintaining a healthy diet, such as the Mediterranean diet, a vegetarian, vegan or another plant-based diet.
• Replacing saturated fat with healthier choices: Clinical trials show that replacing saturated fat with polyunsaturated vegetable oil reduced CVD by 30%. Prospective observational studies show that in many populations lower intake of saturated fat coupled with higher intake of polyunsaturated and monounsaturated fat is associated with lower rates of CVD.
• Decrease body fat if overweight or obese. The effect of weight loss is often difficult to distinguish from dietary change, and evidence on weight reducing diets is limited. In observational studies of people with severe obesity, weight loss following bariatric surgery is associated with a 46% reduction in cardiovascular risk.
• Limit alcohol consumption to the recommended daily limits. People who moderately consume alcoholic drinks have a 25–30% lower risk of cardiovascular disease. However, people who are genetically predisposed to consume less alcohol have lower rates of cardiovascular disease suggesting that alcohol itself may not be protective. Excessive alcohol intake increases the risk of cardiovascular disease and consumption of alcohol is associated with increased risk of a cardiovascular event in the day following consumption.
• Decrease non-HDL cholesterol. Statin treatment reduces cardiovascular mortality by about 31%.
• Stopping smoking and avoidance of second-hand smoke.^[96] Stopping smoking reduces risk by about 35%.
• At least 150 minutes (2 hours and 30 minutes) of moderate exercise per week.
• Lower blood pressure, if elevated. A 10 mmHg reduction in blood pressure reduces risk by about 20%. Lowering blood pressure appears to be effective even at normal blood pressure ranges.
• Decrease psychosocial stress. This measure may be complicated by imprecise definitions of what constitute psychosocial interventions. Mental stress–induced myocardial ischemia is associated with an increased risk of heart problems in those with previous heart disease. Severe emotional and physical stress leads to a form of heart dysfunction known as Takotsubo syndrome in some people. Stress, however, plays a relatively minor role in hypertension. Specific relaxation therapies are of unclear benefit.
• Not enough sleep also raises the risk of high blood pressure. Adults need about 7–9 hours of sleep. Sleep apnea is also a major risk as it causes breathing to stop briefly, which can put stress on the body which can raise the risk of heart disease.

Most guidelines recommend combining preventive strategies. There is some evidence that interventions aiming to reduce more than one cardiovascular risk factor may have beneficial effects on blood pressure, body mass index and waist circumference; however, evidence was limited and the authors were unable to draw firm conclusions on the effects on cardiovascular events and mortality.

There is additional evidence to suggest that providing people with a cardiovascular disease risk score may reduce risk factors by a small amount compared to usual care. However, there was some uncertainty as to whether providing these scores had any effect on cardiovascular disease events. It is unclear whether or not dental care in those with periodontitis affects their risk of cardiovascular disease. According to a 2021 WHO study, working 55+ hours a week raises the risk of stroke by 35% and the risk of dying from heart conditions by 17%, when compared to a 35-40 hours week.

Diet

See also: Lipid hypothesis, Saturated fat and cardiovascular disease, and Salt and cardiovascular disease

A diet high in fruits and vegetables decreases the risk of cardiovascular disease and death.

A 2021 review found that plant-based diets can provide a risk reduction for CVD if a healthy plant-based diet is consumed. Unhealthy plant-based diets do not provide benefits over diets including meat. A similar meta-analysis and systematic review also looked into dietary patterns and found "that diets lower in animal foods and unhealthy plant foods, and higher in healthy plant foods are beneficial for CVD prevention". A 2018 meta-analysis of observational studies concluded that "In most countries, a vegan diet is associated with a more favourable cardio-metabolic profile compared to an omnivorous diet."

Evidence suggests that the Mediterranean diet may improve cardiovascular outcomes. There is also evidence that a Mediterranean diet may be more effective than a low-fat diet in bringing about long-term changes to cardiovascular risk factors (e.g., lower cholesterol level and blood pressure).

The DASH diet (high in nuts, fish, fruits and vegetables, and low in sweets, red meat and fat) has been shown to reduce blood pressure, lower total and low density lipoprotein cholesterol and improve metabolic syndrome; but the long-term benefits have been questioned. A high-fiber diet is associated with lower risks of cardiovascular disease.

Worldwide, dietary guidelines recommend a reduction in saturated fat, and although the role of dietary fat in cardiovascular disease is complex and controversial there is a long-standing consensus that replacing saturated fat with unsaturated fat in the diet is sound medical advice. Total fat intake has not been found to be associated with cardiovascular risk. A 2020 systematic review found moderate quality evidence that reducing saturated fat intake for at least 2 years caused a reduction in cardiovascular events. A 2015 meta-analysis of observational studies however did not find a convincing association between saturated fat intake and cardiovascular disease. Variation in what is used as a substitute for saturated fat may explain some differences in findings. The benefit from replacement with polyunsaturated fats appears greatest, while replacement of saturated fats with carbohydrates does not appear to have a beneficial effect. A diet high in trans fatty acids is associated with higher rates of cardiovascular disease, and in 2015 the Food and Drug Administration (FDA) determined that there was 'no longer a consensus among qualified experts that partially hydrogenated oils (PHOs), which are the primary dietary source of industrially produced trans fatty acids (IP-TFA), are generally recognized as safe (GRAS) for any use in human food'. There is conflicting evidence concerning whether dietary supplements of omega-3 fatty acids (a type of polyunsaturated essential fatty acid) added to diet improve cardiovascular risk.

The benefits of recommending a low-salt diet in people with high or normal blood pressure are not clear. In those with heart failure, after one study was left out, the rest of the trials show a trend to benefit. Another review of dietary salt concluded that there is strong evidence that high dietary salt intake increases blood pressure and worsens hypertension, and that it increases the number of cardiovascular disease events; both as a result of the increased blood pressure and probably through other mechanisms. Moderate evidence was found that high salt intake increases cardiovascular mortality; and some evidence was found for an increase in overall mortality, strokes, and left ventricular hypertrophy.

Intermittent fasting

Overall, the current body of scientific evidence is uncertain on whether intermittent fasting could prevent cardiovascular disease. Intermittent fasting may help people lose more weight than regular eating patterns, but was not different from energy restriction diets.

Medication

Blood pressure medication reduces cardiovascular disease in people at risk, irrespective of age, the baseline level of cardiovascular risk, or baseline blood pressure. The commonly-used drug regimens have similar efficacy in reducing the risk of all major cardiovascular events, although there may be differences between drugs in their ability to prevent specific outcomes. Larger reductions in blood pressure produce larger reductions in risk, and most people with high blood pressure require more than one drug to achieve adequate reduction in blood pressure. Adherence to medications is often poor, and while mobile phone text messaging has been tried to improve adherence, there is insufficient evidence that it alters secondary prevention of cardiovascular disease.

Statins are effective in preventing further cardiovascular disease in people with a history of cardiovascular disease. As the event rate is higher in men than in women, the decrease in events is more easily seen in men than women. In those at risk, but without a history of cardiovascular disease (primary prevention), statins decrease the risk of death and combined fatal and non-fatal cardiovascular disease. The benefit, however, is small. A United States guideline recommends statins in those who have a 12% or greater risk of cardiovascular disease over the next ten years. Niacin, fibrates and CETP Inhibitors, while they may increase HDL cholesterol do not affect the risk of cardiovascular disease in those who are already on statins. Fibrates lower the risk of cardiovascular and coronary events, but there is no evidence to suggest that they reduce all-cause mortality.

Anti-diabetic medication may reduce cardiovascular risk in people with Type 2 diabetes, although evidence is not conclusive. A meta-analysis in 2009 including 27,049 participants and 2,370 major vascular events showed a 15% relative risk reduction in cardiovascular disease with more-intensive glucose lowering over an average follow-up period of 4.4 years, but an increased risk of major hypoglycemia.

Aspirin has been found to be of only modest benefit in those at low risk of heart disease, as the risk of serious bleeding is almost equal to the protection against cardiovascular problems. In those at very low risk, including those over the age of 70, it is not recommended. The United States Preventive Services Task Force recommends against use of aspirin for prevention in women less than 55 and men less than 45 years old; however, it is recommended for some older people.

The use of vasoactive agents for people with pulmonary hypertension with left heart disease or hypoxemic lung diseases may cause harm and unnecessary expense.

Antibiotics for secondary prevention of coronary heart disease

Antibiotics may help patients with coronary disease to reduce the risk of heart attacks and strokes. However, evidence in 2021 suggests that antibiotics for secondary prevention of coronary heart disease are harmful, with increased mortality and occurrence of stroke; the use of antibiotics is not supported for preventing secondary coronary heart disease.

Physical activity

Exercise-based cardiac rehabilitation following a heart attack reduces the risk of death from cardiovascular disease and leads to less hospitalizations. There have been few high-quality studies of the benefits of exercise training in people with increased cardiovascular risk but no history of cardiovascular disease.

A systematic review estimated that inactivity is responsible for 6% of the burden of disease from coronary heart disease worldwide. The authors estimated that 121,000 deaths from coronary heart disease could have been averted in Europe in 2008 if people had not been physically inactive. Low-quality evidence from a limited number of studies suggest that yoga has beneficial effects on blood pressure and cholesterol. Tentative evidence suggests that home-based exercise programs may be more efficient at improving exercise adherence.

Dietary supplements

While a healthy diet is beneficial, the effect of antioxidant supplementation (vitamin E, vitamin C, etc.) or vitamins has not been shown to protect against cardiovascular disease and in some cases may possibly result in harm. Mineral supplements have also not been found to be useful. Niacin, a type of vitamin B3, may be an exception with a modest decrease in the risk of cardiovascular events in those at high risk. Magnesium supplementation lowers high blood pressure in a dose-dependent manner. Magnesium therapy is recommended for people with ventricular arrhythmia associated with torsades de pointes who present with long QT syndrome, and for the treatment of people with digoxin intoxication-induced arrhythmias. There is no evidence that omega-3 fatty acid supplementation is beneficial. A 2022 review found that some dietary supplements, including micronutrients, may reduce risk factors for cardiovascular disease.

Management

Cardiovascular disease is treatable with initial treatment primarily focused on diet and lifestyle interventions. Influenza may make heart attacks and strokes more likely and therefore influenza vaccination may decrease the chance of cardiovascular events and death in people with heart disease.

Proper CVD management necessitates a focus on MI and stroke cases due to their combined high mortality rate, keeping in mind the cost-effectiveness of any intervention, especially in developing countries with low or middle-income levels. Regarding MI, strategies using aspirin, atenolol, streptokinase or tissue plasminogen activator have been compared for quality-adjusted life-year (QALY) in regions of low and middle income. The costs for a single QALY for aspirin and atenolol were less than US$25, streptokinase was about $680, and t-PA was $16,000. Aspirin, ACE inhibitors, beta-blockers, and statins used together for secondary CVD prevention in the same regions showed single QALY costs of $350.

There are also surgical or procedural interventions that can save someone's life or prolong it. For heart valve problems, a person could have surgery to replace the valve. For arrhythmias, a pacemaker can be put in place to help reduce abnormal heart rhythms and for a heart attack, there are multiple options two of these are a coronary angioplasty and a coronary artery bypass surgery.

There is probably no additional benefit in terms of mortality and serious adverse events when blood pressure targets were lowered to ≤ 135/85 mmHg from ≤ 140 to 160/90 to 100 mmHg.

Epidemiology

Cardiovascular diseases deaths per million persons in 2012

  318–925

  926–1,148

  1,149–1,294

  1,295–1,449

  1,450–1,802

  1,803–2,098

  2,099–2,624

  2,625–3,203

  3,204–5,271

  5,272–10233

Disability-adjusted life year for cardiovascular diseases per 100,000 inhabitants in 2004

  no data

  <900

  900–1650

  1650–2300

  2300–3000

  3000–3700

  3700–4400

  4400–5100

  5100–5800

  5800–6500

  6500–7200

  7200–7900

  >7900

Cardiovascular diseases are the leading cause of death worldwide and in all regions except Africa. In 2008, 30% of all global death was attributed to cardiovascular diseases. Death caused by cardiovascular diseases are also higher in low- and middle-income countries as over 80% of all global deaths caused by cardiovascular diseases occurred in those countries. It is also estimated that by 2030, over 23 million people will die from cardiovascular diseases each year.

It is estimated that 60% of the world's cardiovascular disease burden will occur in the South Asian subcontinent despite only accounting for 20% of the world's population. This may be secondary to a combination of genetic predisposition and environmental factors. Organizations such as the Indian Heart Association are working with the World Heart Federation to raise awareness about this issue.

Research

See also: Heart-on-a-chip and Vessel-on-a-chip

There is evidence that cardiovascular disease existed in pre-history, and research into cardiovascular disease dates from at least the 18th century. The causes, prevention, and/or treatment of all forms of cardiovascular disease remain active fields of biomedical research, with hundreds of scientific studies being published on a weekly basis.

Recent areas of research include the link between inflammation and atherosclerosis the potential for novel therapeutic interventions, and the genetics of coronary heart disease.

Trans fat

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Trans_fat

Margarine, which can contain trans fat.

Trans fat, also called trans-unsaturated fatty acids, or trans fatty acids, is a type of unsaturated fat that occurs in foods. Trace concentrations of trans fats occur naturally, but large amounts are found in some processed foods. Since consumption of trans fats is unhealthy, artificial trans fats are highly regulated or banned in many nations. However, they are still widely consumed in developing nations, resulting in hundreds of thousands of deaths each year. The World Health Organization (WHO) had set a goal to make the world free from industrially produced trans fat by the end of 2023. The goal was not met, and the WHO announced another goal "for accelerated action till 2025 to complete this effort" along with associated support on 1 February 2024.

Occurrence

Some trans fats arise naturally, and some are the result of human actions.

Naturally-occurring trans fats

Vaccenic acid, a naturally occurring trans fatty acid, comprises 0.4–4% of the total fatty acid content in dairy milk.

Trans fats occur in meat and dairy products from ruminants. For example, butter contains about 3% trans fat. These naturally occurring trans fats include conjugated linoleic acid (CLA) and vaccenic acid. They arise from the action of bacteria in the rumen. In contrast to industrially produced trans fats, the bacterial produced versions exist only as a few isomers. Polyunsaturated fats are toxic to the rumen-based bacteria, which induces the latter to detoxify the fats by changing some cis-double bonds to trans. As industrial sources of trans fats are eliminated, increased attention focuses on ruminant derived trans fats.

The trans fatty acid vaccenic acid has health benefits. Small amounts occur in meat and milk fat.

Hydrogenation

Main article: Hydrogenation

Trans fat can be an unintentional byproduct of the industrial processing of oils. Unlike naturally derived trans fats, the trans fats that result from hydrogenation consist of many isomers. In food production, liquid cis-unsaturated fats such as vegetable oils are hydrogenated to produce more saturated fats, which have desirable properties:

• The shelf life of fats correlates with the degree of saturation: polyunsaturated fats are prone to autoxidation whereas saturated fats, being virtually inert in air, have very long shelf lives.
• Saturated fats tend to be more solid at room temperature. This property is important for margarine, one of the original uses for fat hydrogenation.

However, an isomerization side reaction during fat hydrogenation can convert remaining unsaturated fats to the thermodynamically-favored trans isomer.

The desirable (left) and undesirable pathways for partial hydrogenation of an unsaturated fat.

A number of old and new ingredients are available to replace partially-hydrogenated oil containing significant levels of trans fat. These include partially-hydrogenated oil made with improved processes, plant oils rich in monounsaturated fats and saturated fats, and a mix of fats combined with interesterification. The technology has improved such that a 2021 review indicates that trans fat from hydrogenated fats is no longer a problem in modern countries.

Thermal isomerization

When heated (cooked), some unsaturated fats change from their normal geometry to trans. The rate of isomerization is accelerated by free radicals.

History

Cover of original Crisco cookbook, 1912

The German chemist Wilhelm Normann showed that liquid oils could be hydrogenated. He patented the process in 1902. During the years 1905–1910, Normann built a fat-hardening facility in the Herford company. At the same time, the invention was extended to a large-scale plant in Warrington, England, at Joseph Crosfield & Sons, Limited. It took only two years until the hardened fat could be successfully produced in the plant in Warrington, commencing production in the autumn of 1909. The initial year's production totalled nearly 3,000 tonnes. In 1909, Procter & Gamble acquired the United States rights to the Normann patent; in 1911, they began marketing the first hydrogenated shortening, Crisco (composed largely of partially hydrogenated cottonseed oil). Further success came from the marketing technique of giving away free cookbooks in which every recipe called for Crisco.

Normann's hydrogenation process made it possible to stabilize affordable whale oil or fish oil for human consumption, a practice kept secret to avoid consumer distaste.

Before 1910, dietary fats in industrialized nations consisted mostly of butterfat, beef tallow, and lard. During Napoleon's reign in France in the early 19th century, a type of margarine was invented to feed troops using tallow and buttermilk. Soybeans began to be imported into the U.S. as a source of protein in the early 20th century, resulting in an abundance of soybean oil as a by-product that could be turned into a solid fat, thereby addressing a shortage of butterfat. Furthermore, with the advent of refrigeration, margarines based on hydrogenated fats presented the advantage that, unlike butter, they could be taken out of a refrigerator and immediately spread on bread. Some minor changes to the chemical composition of hydrogenated fats yielded superior baking properties compared to lard. As a result of these factors, margarine made from partially hydrogenated soybean oil began to replace butterfat. Partially hydrogenated fat such as Crisco and Spry, sold in England, began to replace butter and lard in baking bread, pies, cookies, and cakes in 1920.

Production of partially hydrogenated fats increased steadily in the 20th century as processed vegetable fats replaced animal fats in the U.S. and other Western countries. At first, the argument was a financial one due to the lower costs of margarines and shortenings compared to lard and butter, particularly for restaurants and manufacturers. However, during the 1980s regulators, physicians, nutritionists, popular health media, educational curricula and cookbooks began to promote diets low in saturated fats for health reasons. Advocacy groups in the U.S. responded by demanding the replacement of saturated animal and tropical fats with vegetable alternatives. The Center for Science in the Public Interest (CSPI) campaigned vigorously against the use of saturated fats by corporations, including fast-food restaurants, endorsing trans fats as a healthier alternative. The National Heart Savers Association took out full page ads in major newspapers, attacking the use of beef tallow in McDonald's French fries. They urged multinational fast-food restaurants and food manufacturers to switch to vegetable oils, and almost all targeted firms responded by replacing saturated fats with trans fats.

Although this shift to trans fats was rooted in health concerns, there were suggestions in the scientific literature as early as 1956 that trans fats themselves could actually be a cause of a large increase in coronary artery disease. Studies in the early 1990s brought renewed scrutiny and confirmation of the negative health impact of trans fats. In 1994, it was estimated that trans fats caused at least 20,000 deaths annually in the U.S. from heart disease. In the 1990s, activists such as CSPI that had promoted trans fat safety began arguing that trans fats should be disclosed on product labels and menus. Several lawsuits were launched against high-visibility restaurants and food manufacturers with the objective of supporting a broader phase-out of trans fats.

Mandatory food labeling was introduced in several countries and Denmark was first to mandate limits on industrially-produced trans fats in 2004. In January 2007, faced with the prospect of an outright ban on the sale of their product, Crisco was reformulated to meet the U.S. Food and Drug Administration (FDA) definition of "zero grams trans fats per serving" (that is less than one gram per tablespoon, or up to 7% by weight; or less than 0.5 grams per serving size) by boosting the saturation and then diluting the resulting solid fat with unsaturated vegetable oils. Noting that elimination of industrially produced trans fat is feasible and achievable, the World Health Organization (WHO) has set a goal to make the world free from industrially produced trans fat by the end of 2023. By the end of 2021, the WHO announced that 40 countries had implemented industrial trans fat elimination policies that "are protecting 1.4 billion people from this deadly food compound" but that 10 of the 15 countries suffering the highest health impacts from trans fats had not yet adopted a policy.

Structure

A fatty acid is characterized as either saturated or unsaturated based on the respective absence or presence of C=C double bonds in its backbone. If the molecule contains no double C=C bonds, it is said to be saturated; otherwise, it is unsaturated to some degree.

The C=C double bond is rotationally rigid. If the hydrogen bonded to each of the carbons in this double bond are on the same side, this is called cis, and leads to a bent molecular chain. If the two hydrogens are on opposite sides, this is called trans, and leads to a straight chain.

Trans unsaturated (Elaidic acid)	Cis unsaturated (Oleic acid)	Saturated (Stearic acid)
Elaidic acid is the main trans unsaturated fatty acid often found in partially hydrogenated vegetable oils.	Oleic acid is a cis unsaturated fatty acid making up 55–80% of olive oil.	Stearic acid is a saturated fatty acid found in animal fats and is the intended product in full hydrogenation. Stearic acid is neither unsaturated nor trans because it has no carbon-carbon double bonds.
These fatty acids are geometric isomers (structurally identical except for the arrangement of the double bond).		This fatty acid contains no carbon-carbon double bonds and is not isomeric with the prior two.

Because trans fats are more linear, they crystallize more easily, allowing them to be solid (rather than liquid) at room temperatures. This has several processing and storage advantages.

In nature, unsaturated fatty acids generally have cis configurations as opposed to trans configurations. Saturated fatty acids (those without any carbon-carbon double bonds) are abundant (see tallow), but they also can be generated from unsaturated fats by the process of fat hydrogenation. In the course of hydrogenation, some cis double bonds convert into trans double bonds. Chemists call this conversion an isomerization reaction.

Wilhelm Normann patented the hydrogenation of liquid oils in 1902

Hydrogenation of an unsaturated fatty acid is intended to convert unsaturated fatty acids (and unsaturated fats) to saturated derivatives. The hydrogenation process however can cause cis C=C bonds to become trans. Typical commercial hydrogenation is partial to obtain a malleable mixture of fats that is solid at room temperature, but melts during baking, or consumption.

The same molecule, containing the same number of atoms, with a double bond in the same location, can be either a trans or a cis fatty acid depending on the configuration of the double bond. For example, oleic acid and elaidic acid are both unsaturated fatty acids with the chemical formula C₉H₁₇C₉H₁₇O₂. They both have a double bond located midway along the carbon chain. It is the configuration of this bond that sets them apart. The configuration has implications for the physical-chemical properties of the molecule. The trans configuration is straighter, while the cis configuration is noticeably kinked as can be seen from the three-dimensional representation shown above. Cis- and trans fatty acids (and their derivatives) have distinct chemical (and metabolic) properties, For example, the melting point of elaidic acid is 45 °C higher than that of oleic acid. This notably means that it is a solid at human body temperatures.

In the sense of food production, however, the goal is not necessarily to simply change the configuration of double bonds while maintaining the same ratios of hydrogen to carbon; rather, the goal is to decrease the number of double bonds (when a fatty acid molecule contains more than one double bond it is classified as "polyunsaturated") by increasing the amount of hydrogen (and, thus, single bonds) in the fatty acid. This subsequent lesser degree of unsaturation (and, simultaneously, greater degree of saturation) thereby changes the consistency of the fatty acid by way of allowing its molecules to more greatly compress and congeal and in turn thereby makes it less prone to rancidity (in which free radicals attack double bonds). In this second sense of the goal being to simply reduce the degree of unsaturation in an unsaturated fatty acid, the production of trans fatty acids is thus an undesirable side effect of partial hydrogenation.

Catalytic partial hydrogenation produces some trans-fats. The standard 140 kPa (20 psi) process of hydrogenation produces a product of about 40% trans fatty acid by weight, compared to about 17% using higher pressures of hydrogen. Blended with unhydrogenated liquid soybean oil, the high-pressure-processed oil produced margarine containing 5 to 6% trans fat. Based on current U.S. labeling requirements (see below), the manufacturer could claim the product was free of trans fat. The level of trans fat may also be altered by modification of the temperature and the length of time during hydrogenation.

The trans fat levels can be quantified using various forms of chromatography.

Presence in food

Trans fat contents in various foods, ranked in g per 100 g

Food type	Trans fat content
shortenings	10–33
margarine, stick	6.2–16.8
butter	2–7
whole milk	0.07–0.1
breads/cake products	0.1–10
cookies and crackers	1–8
tortilla chips	5.8
cake frostings, sweets	0.1–7
animal fat	0–5
ground beef	1

A type of trans fat occurs naturally in the milk and body fat of ruminants (such as cattle and sheep) at a level of 2–5% of total fat. Natural trans fats, which include conjugated linoleic acid (CLA) and vaccenic acid, originate in the rumen of these animals. CLA has two double bonds, one in the cis configuration and one in trans, which makes it simultaneously a cis- and a trans-fatty acid.

Animal-based fats were once the only trans fats consumed, but by far the largest amount of trans fat consumed today is created by the processed food industry as a side effect of partially hydrogenating unsaturated plant fats (generally vegetable oils). These partially hydrogenated fats have displaced natural solid fats and liquid oils in many areas, the most notable ones being in the fast food, snack food, fried food, and baked goods industries.

Partially hydrogenated oils have been used in food for many reasons. Hydrogenation increases product shelf life and decreases refrigeration requirements. Many baked foods require semi-solid fats to suspend solids at room temperature; partially hydrogenated oils have the right consistency to replace animal fats such as butter and lard at lower cost. They are also an inexpensive alternative to other semi-solid oils such as palm oil.

Reaction scheme: Trans fat is created as a side effect of partially catalytic hydrogenation of unsaturated plant fats (generally vegetable oils) with cis carbon-carbon double bonds.

Up to 45% of the total fat in those foods containing human-made trans fats formed by partially hydrogenating plant fats may be trans fat. Baking shortenings, unless reformulated, contain around 30% trans fats compared to their total fats. High-fat dairy products such as butter contain about 4%. Margarines not reformulated to reduce trans fats may contain up to 15% trans fat by weight, but some reformulated ones are less than 1% trans fat.

It has been established that trans fats in human breast milk fluctuate with maternal consumption of trans fat, and that the amount of trans fats in the bloodstream of breastfed infants fluctuates with the amounts found in their milk. In 1999, reported percentages of trans fats (compared to total fats) in human milk ranged from 1% in Spain, 2% in France, 4% in Germany, and 7% in Canada and the U.S.

Trans fats are used in shortenings for deep-frying in restaurants, as they can be used for longer than most conventional oils before becoming rancid. In the early 21st century, non-hydrogenated vegetable oils that have lifespans exceeding that of the frying shortenings became available. As fast-food chains routinely use different fats in different locations, trans fat levels in fast food can have large variations. For example, an analysis of samples of McDonald's French fries collected in 2004 and 2005 found that fries served in New York City contained twice as much trans fat as in Hungary, and 28 times as much as in Denmark, where trans fats are restricted. At KFC, the pattern was reversed, with Hungary's product containing twice the trans fat of the New York product. Even within the U.S. there was variation, with fries in New York containing 30% more trans fat than those from Atlanta.

Nutritional guidelines

The National Academy of Sciences (NAS) advises the U.S. and Canadian governments on nutritional science for use in public policy and product labeling programs. Their 2002 Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids contains their findings and recommendations regarding consumption of trans fat (summary).

Their recommendations are based on two key facts. First, "trans fatty acids are not essential and provide no known benefit to human health", whether of animal or plant origin. Second, while both saturated and trans fats increase levels of low-density lipoprotein (LDL), trans fats also lower levels of high-density lipoprotein (HDL), thus increasing the risk of coronary artery disease. The NAS is concerned "that dietary trans fatty acids are more deleterious with respect to coronary artery disease than saturated fatty acids". This analysis is supported by a 2006 New England Journal of Medicine scientific review that states "from a nutritional standpoint, the consumption of trans fatty acids results in considerable potential harm but no apparent benefit."

Because of these facts and concerns, the NAS has concluded there is no safe level of trans fat consumption. There is no adequate level, recommended daily amount or tolerable upper limit for trans fats. This is because any incremental increase in trans fat intake increases the risk of coronary artery disease.

Despite this concern, the NAS dietary recommendations have not included eliminating trans fat from the diet. This is because trans fat is naturally present in many animal foods in trace quantities, and thus its removal from ordinary diets might introduce undesirable side effects and nutritional imbalances if proper nutritional planning is not undertaken. The NAS has, thus, "recommended that trans fatty acid consumption be as low as possible while consuming a nutritionally adequate diet". Like the NAS, the World Health Organization has tried to balance public health goals with a practical level of trans fat consumption, recommending in 2003 that trans fats be limited to less than 1% of overall energy intake.

The US National Dairy Council has asserted that the trans fats present in foods of animal origin are of a different type than those in partially hydrogenated oils, and do not appear to exhibit the same negative effects. A scientific review agrees with the conclusion (stating that "the sum of the current evidence suggests that the Public health implications of consuming trans fats from ruminant products are relatively limited") but cautions that this may be due to the low consumption of trans fats from animal sources compared to artificial ones.

A meta-analysis showed that all trans fats, regardless of natural or artificial origin equally raise LDL and lower HDL levels. Other studies though have shown different results when it comes to animal based trans fats like conjugated linoleic acid (CLA). Although CLA is known for its anticancer properties, researchers have also found that the cis-9, trans-11 form of CLA can reduce the risk for cardiovascular disease and help fight inflammation.

Health risks

Partially hydrogenated vegetable oils were an increasingly significant part of the human diet for about 100 years, especially after 1950 as processed food rose in popularity. The deleterious effects of trans fat consumption are scientifically accepted.

Intake of dietary trans fat disrupts the body's ability to metabolize essential fatty acids (EFAs, including Omega-3) leading to changes in the phospholipid fatty acid composition of the arterial walls, thereby raising risk of coronary artery disease.

While the mechanisms through which trans fatty acids contribute to coronary artery disease are understood, the mechanism for their effects on diabetes is still under investigation. They may impair the metabolism of long-chain polyunsaturated fatty acids (LCPUFAs), but maternal pregnancy trans fatty acid intake has been inversely associated with LCPUFAs levels in infants at birth thought to underlie the positive association between breastfeeding and intelligence.

Consumption of industrial trans fat in the form of partially hydrogenated oil causes many health problems. They were abundant in fast food restaurants. They are consumed in greater quantities by people who lack access to a diet consisting of fewer partially-hydrogenated fats, or who often consume fast food. A diet high in trans fats can contribute to obesity, high blood pressure, and higher risk for heart disease. Trans fat is also implicated in Type 2 diabetes.

Coronary artery disease

The most important health risk identified for trans fat consumption is an elevated risk of coronary artery disease (CAD). A 1994 study estimated that over 30,000 cardiac deaths per year in the U.S. are attributable to the consumption of trans fats. By 2006 upper estimates of 100,000 deaths were suggested. A comprehensive review of studies of trans fats published in 2006 in the New England Journal of Medicine reports a strong and reliable connection between trans fat consumption and CAD, concluding that "On a per-calorie basis, trans fats appear to increase the risk of CAD more than any other macronutrient, conferring a substantially increased risk at low levels of consumption (1 to 3% of total energy intake)".

The major evidence for the effect of trans fat on CAD comes from the Nurses' Health Study – a cohort study that has been following 120,000 female nurses since its inception in 1976. In this study, Hu and colleagues analyzed data from 900 coronary events from the study's population during 14 years of followup. He determined that a nurse's CAD risk roughly doubled (relative risk of 1.93, CI: 1.43 to 2.61) for each 2% increase in trans fat calories consumed (instead of carbohydrate calories). By contrast, for each 5% increase in saturated fat calories (instead of carbohydrate calories) there was a 17% increase in risk (relative risk of 1.17, CI: 0.97 to 1.41). "The replacement of saturated fat or trans unsaturated fat by cis (unhydrogenated) unsaturated fats was associated with larger reductions in risk than an isocaloric replacement by carbohydrates." Hu also reports on the benefits of reducing trans fat consumption. Replacing 2% of food energy from trans fat with non-trans unsaturated fats more than halves the risk of CAD (53%). By comparison, replacing a larger 5% of food energy from saturated fat with non-trans unsaturated fats reduces the risk of CAD by 43%.

Another study considered deaths due to CAD, with consumption of trans fats being linked to an increase in mortality, and consumption of polyunsaturated fats being linked to a decrease in mortality.

There are two accepted tests that measure an individual's risk for coronary artery disease, both blood tests. The first considers ratios of two types of cholesterol, the other the amount of a cell-signalling cytokine called C-reactive protein. The ratio test is more accepted, while the cytokine test may be more powerful but is still being studied. The effect of trans fat consumption has been documented on each as follows:

• Cholesterol ratio: This ratio compares the levels of LDL to HDL. Trans fat behaves like saturated fat by raising the level of LDL, but, unlike saturated fat, it has the additional effect of decreasing levels of HDL. The net increase in LDL/HDL ratio with trans fat is approximately double that due to saturated fat. (Higher ratios are worse.) One randomized crossover study published in 2003 comparing the effect of eating a meal on blood lipids of (relatively) cis and trans fat rich meals showed that cholesteryl ester transfer (CET) was 28% higher after the trans meal than after the cis meal and that lipoprotein concentrations were enriched in apolipoprotein(a) after the trans meals.
• C-reactive protein (CRP): A study of over 700 nurses showed that those in the highest quartile of trans fat consumption had blood levels of CRP that were 73% higher than those in the lowest quartile.

Other health risks

Scientific studies have examined other negative effects of industrial trans fat beyond cardiovascular disease, with the next most studied area being type-2 diabetes.

• Alzheimer's disease: A study published in Archives of Neurology in February 2003 suggested that the intake of both trans fats and saturated fats promote the development of Alzheimer disease, although not confirmed in an animal model. It has been found that trans fats impaired memory and learning in middle-age rats. The trans-fat eating rats' brains had fewer proteins critical to healthy neurological function and inflammation in and around the hippocampus, the part of the brain responsible for learning and memory. These are the exact types of changes normally seen at the onset of Alzheimer's, but seen after six weeks, even though the rats were still young. A systematic review of five articles based on four prospective cohort studies of individuals did not find a robust association between their intake of trans fatty acids and development of Alzheimer's disease (or several other forms of dementia). The review based this conclusion on finding that 4 of the 5 reports appeared biased and therefore recommended more well-designed prospective studies to clarify this issue.
• Cancer: In 2007 the American Cancer Society stated that a relationship between trans fats and cancer "has not been determined." One study has found a positive connection between trans fat and prostate cancer. However, a larger study found a correlation between trans fats and a significant decrease in high-grade prostate cancer. An increased intake of trans fatty acids may raise the risk of breast cancer by 75%, suggest the results from the French part of the European Prospective Investigation into Cancer and Nutrition.
• Diabetes: There is a growing concern that the risk of type 2 diabetes increases with trans fat consumption. However, consensus has not been reached. For example, one study found that risk is higher for those in the highest quartile of trans fat consumption. Another study has found no diabetes risk once other factors such as total fat intake and BMI were accounted for.
• Obesity: Research indicates that trans fat may increase weight gain and abdominal fat, despite a similar caloric intake. A 6-year experiment revealed that monkeys fed a trans fat diet gained 7.2% of their body weight, as compared to 1.8% for monkeys on a mono-unsaturated fat diet. Although obesity is frequently linked to trans fat in the popular media, this is generally in the context of eating too many calories; there is not a strong scientific consensus connecting trans fat and obesity, although the 6-year experiment did find such a link, concluding that "under controlled feeding conditions, long-term TFA consumption was an independent factor in weight gain. TFAs enhanced intra-abdominal deposition of fat, even in the absence of caloric excess, and were associated with insulin resistance, with evidence that there is impaired post-insulin receptor binding signal transduction."
• Liver dysfunction: Trans fats are metabolized differently by the liver than other fats and interfere with delta 6 desaturase. Delta 6 desaturase is an enzyme involved in converting essential fatty acids to arachidonic acid and prostaglandins, both of which are important to the functioning of cells.
• Infertility in women: One 2007 study found, "Each 2% increase in the intake of energy from trans unsaturated fats, as opposed to that from carbohydrates, was associated with a 73% greater risk of ovulatory infertility...".
• Major depressive disorder: Spanish researchers analysed the diets of 12,059 people over six years and found that those who ate the most trans fats had a 48 per cent higher risk of depression than those who did not eat trans fats. One mechanism may be trans-fats' substitution for docosahexaenoic acid (DHA) levels in the orbitofrontal cortex (OFC). Very high intake of trans-fatty acids (43% of total fat) in mice from 2 to 16 months of age was associated with lowered DHA levels in the brain (p=0.001). When the brains of 15 major depressive subjects who had committed suicide were examined post-mortem and compared against 27 age-matched controls, the suicidal brains were found to have 16% less (male average) to 32% less (female average) DHA in the OFC. The OFC controls reward, reward expectation, and empathy (all of which are reduced in depressive mood disorders) and regulates the limbic system.
• Behavioral irritability and aggression: a 2012 observational analysis of subjects of an earlier study found a strong relation between dietary trans fat acids and self-reported behavioral aggression and irritability, suggesting but not establishing causality.
• Diminished memory: In a 2015 article, researchers re-analyzing results from the 1999-2005 UCSD Statin Study argue that "greater dietary trans fatty acid consumption is linked to worse word memory in adults during years of high productivity."
• Acne: According to a 2015 study, trans fats are one of several components of Western pattern diets which promote acne, along with carbohydrates with high glycemic load such as refined sugars or refined starches, milk and dairy products, and saturated fats, while omega-3 fatty acids, which reduce acne, are deficient in Western pattern diets.

Public response and regulation

Main article: Trans fat regulation

International

The international trade in food is standardized in the Codex Alimentarius. Hydrogenated oils and fats come under the scope of Codex Stan 19. Non-dairy fat spreads are covered by Codex Stan 256-2007. In the Codex Alimentarius, trans fat to be labelled as such is defined as the geometrical isomers of monounsaturated and polyunsaturated fatty acids having non-conjugated [interrupted by at least one methylene group (−CH₂−)] carbon-carbon double bonds in the trans configuration. This definition excludes specifically the trans fats (vaccenic acid and conjugated linoleic acid) that are present especially in human milk, dairy products, and beef.

In 2018 the World Health Organization launched a plan to eliminate trans fat from the global food supply. They estimate that trans fat leads to more than 500,000 deaths from cardiovascular disease yearly.

Argentina

Trans fat content labeling is required starting in August 2006. Since 2010, vegetable oils and fats sold to consumers directly must contain only 2% of trans fat over total fat, and other food must contain less than 5% of their total fat.^[109] Starting on 10 December 2014, Argentina has on effect a total ban on food with trans fat, a regulation the government estimated could save them more than US$100 million a year on healthcare.^[110]

Australia

The former federal assistant health minister, Christopher Pyne, asked fast food outlets to reduce their trans fat use. A draft plan was proposed, with a September 2007 timetable, to reduce reliance on trans fats and saturated fats.

As of 2018, Australia's food labeling laws do not require trans fats to be shown separately from the total fat content. However, margarine in Australia has been mostly free of trans fat since 1996.

Austria

Trans fat content is limited to 4% of total fat, or 2% on products that contain more than 20% fat.^[113]

Belgium

The Conseil Supérieur de la Santé published in 2012 a science-policy advisory report on industrially produced trans fatty acids that focuses on the general population. Its recommendation to the legislature was to prohibit more than 2 g of trans fatty acids per 100 g of fat in food products.

Brazil

Resolution 360, dated December 23, 2003, by the Brazilian ministry of health required the amount of trans fat to be specified in labels of food products. On 31 July 2006, such labeling of trans fat contents became mandatory. In 2019 Anvisa published a new legislation to reduce the total amount of trans fat in any industrialized food sold in Brazil to a maximum of 2% by the end of 2023.

Since January 1, 2023, the use, production and import of hydrogenated vegetable oils in food for consumption has been completely banned by Anvisa.

Canada

In a process that began in 2004, Health Canada finally banned partially hydrogenated oils (PHOs), the primary source of industrially produced trans fats in foods, in September 2018.

On 15 September 2017, Health Canada announced that trans fat would be completely banned effective on 15 September 2018. The ban came into effect in September 2018, banning partially hydrogenated oils (the largest source of industrially produced trans fats in foods). It is now illegal for manufacturers to add partially hydrogenated oils to foods sold in or imported into Canada.

Public perception

A cross-sectional study was conducted in Regina, Saskatchewan in February 2009 at 3 different grocery stores located in 3 different regions that had the same median income before taxes of around $30,000. Of the 211 respondents to the study, most were women who purchased most of the food for their household. When asked how they decide what food to buy, the most important factors were price, nutritional value, and need. When looking at the nutritional facts, however, they indicated that they looked at the ingredients, and neglected to pay attention to the amount of trans fat. This means that trans fat is not on their minds unless they are specifically told of it. When asked if they ever heard about trans fat, 98% said, "Yes." However, only 27% said that it was unhealthy. Also, 79% said that they only knew a little about trans fats, and could have been more educated.

Respondents aged 41–60 were more likely to view trans fat as a major health concern, compared to ages 18–40. When asked if they would stop buying their favorite snacks if they knew it contained trans fat, most said they would continue purchasing it, especially the younger respondents. Also, of the respondents that called trans fat a major concern, 56% of them still would not change their diet to non-trans fat snacks. This is because taste and food gratification take precedence over perceived risk to health. "The consumption of trans fats and the associated increased risk of CHD is a public health concern regardless of age and socioeconomic status".

Denmark

Denmark became the first country to introduce laws strictly regulating the sale of many foods containing trans fats in March 2003, a move that effectively bans partially hydrogenated oils. The limit is 2% of fats and oils destined for human consumption. This restriction is on the ingredients rather than the final products. This regulatory approach has made Denmark the first country in which it is possible to eat "far less" than 1 g of industrially produced trans fats daily, even with a diet including prepared foods. It is hypothesized that the Danish government's efforts to decrease trans fat intake from 6 g to 1 g per day over 20 years is related to a 50% decrease in deaths from ischemic heart disease.

European Union

In 2004, the European Food Safety Authority produced a scientific opinion on trans fatty acids, surmising that "higher intakes of TFA may increase risk for coronary heart disease".

From 2 April 2021 foods in the EU intended for consumers are required to contain less than 2g of industrial trans fat per 100g of fat.

Greece

Law in Greece limits content of trans fats sold in school canteens to 0.1% (Ministerial Decision Υ1γ/ΓΠ/οικ 81025/ΦΕΚ 2135/τ.Β'/29-08-2013 as modified by Ministerial Decision Υ1γ/ Γ.Π/οικ 96605/ΦΕΚ 2800 τ.Β/4-11-201).

Iceland

Total trans fat content was limited in 2010 to 2% of total fat content.

Israel

Since 2014, it is obligatory to mark food products with more than 2% (by weight) fat. The nutritional facts must contain the amount of trans fats.

Pakistan

Ministry of National Health Services Regulations and Coordination, Government of Pakistan with the support of WHO has taken the initiative to eliminate trans fat from food chain in Pakistan. Vanaspati Ghee (partially hydrogenated fat) and margarine have been identified as major dietary vectors for trans fat. PSQCA (Pakistan Standard and Quality Control Authority) has set the deadline for the reduction of trans fat level as per recommendations of WHO by June 2023.

Philippines

The Department of Health has reminded food companies to reformulate and remove industrially produced trans fatty acids (TFA) from their products by June 18, 2023. It said that non-communicable diseases (NCDs) such as cardiovascular disease have been one of the leading causes of death in the country. All product formulations and labels of prepackaged processed food with industrially-produced TFA must comply with the guidelines stated in the DOH Administrative Order No. 2021-0039 and the FDA Circular No. 2021- 0028. Violation of any of the provisions of the administrative order and the FDA circular would be grounds for the disapproval, suspension, or cancellation of the certificate of product registration of concerned food manufacturers.

Saudi Arabia

The Saudi Food and Drug Authority (SFDA) requires importers and manufacturers to write trans fats amounts in the nutritional facts labels of food products according to the requirements of Saudi Standard Specifications/Gulf Specifications. Starting in 2020, Saudi Minister of Health announced the ban of trans fat in all food products due to their health risks.

Singapore

The Ministry of Health announced on 6 March 2019 that partially-hydrogenated oils (PHOs) will be banned. A target is set to ban PHOs by June 2021, aiming to encourage healthy eating habits.

Sweden

The parliament gave the government a mandate in 2011 to submit without delay a law prohibiting the use of industrially produced trans fats in foods, as of 2017 the law has not yet been implemented.

Switzerland

Switzerland followed Denmark's trans fats ban, and implemented its own starting in April 2008.

United Kingdom

In October 2005, the Food Standards Agency (FSA) asked for better labelling in the UK. In the edition of 29 July 2006 of the British Medical Journal, an editorial also called for better labelling. In January 2007, the British Retail Consortium announced that major UK retailers, including Asda, Boots, Co-op Food, Iceland, Marks and Spencer, Sainsbury's, Tesco and Waitrose intended to cease adding trans fatty acids to their own products by the end of 2007.

Sainsbury's became the first UK major retailer to ban all trans fat from all their own store brand foods.

On 13 December 2007, the Food Standards Agency issued news releases stating that voluntary measures to reduce trans fats in food had already resulted in safe levels of consumer intake.

On 15 April 2010, a British Medical Journal editorial called for trans fats to be "virtually eliminated in the United Kingdom by next year".

The June 2010 National Institute for Health and Clinical Excellence (NICE) report Prevention of cardiovascular disease declared that 40,000 cardiovascular disease deaths in 2006 were "mostly preventable". To achieve this, NICE offered 24 recommendations including product labelling, public education, protecting under–16s from marketing of unhealthy foods, promoting exercise and physically active travel, and even reforming the Common Agricultural Policy to reduce production of unhealthy foods. Fast-food outlets were mentioned as a risk factor, with (in 2007) 170 g of McDonald's fries and 160 g nuggets containing 6 to 8 g of trans fats, conferring a substantially increased risk of coronary artery disease death. NICE made three specific recommendation for diet: (1) reduction of dietary salt to 3 g per day by 2025; (2) halving consumption of saturated fats; and (3) eliminating the use of industrially produced trans fatty acids in food. However, the recommendations were greeted unhappily by the food industry, which stated that it was already voluntarily dropping the trans fat levels to below the WHO recommendations of a maximum of 2%.

Rejecting an outright ban, the Health Secretary Andrew Lansley launched on 15 March 2012 a voluntary pledge to remove artificial trans fats by the end of the year. Asda, Pizza Hut, Burger King, Tesco, Unilever and United Biscuits are some of 73 businesses who have agreed to do so. Lansley and his special Adviser Bill Morgan formerly worked for firms with interests in the food industry and some journalists have alleged that this results in a conflict of interest. Many health professionals are not happy with the voluntary nature of the deal. Simon Capewell, Professor of Clinical Epidemiology at the University of Liverpool, felt that justifying intake on the basis of average figures was unsuitable since some members of the community could considerably exceed this.

United States

Before 1 January 2006, consumers in the U.S. could not always determine the presence, or quantity, of trans fats from partially hydrogenated oils in food products, because this information was not required on the ingredient list before that date. In 2010, according to the FDA, the average American consumed 5.8 grams of trans fat per day (2.6% of energy intake). Monoglycerides and diglycerides are not considered fats by the FDA, despite their nearly equal calorie per weight contribution during ingestion.

On 11 July 2003, the FDA issued a regulation requiring manufacturers to list trans fat on the Nutrition Facts panel of foods and some dietary supplements. The new labeling rule became mandatory across the board on 1 January 2006, even for companies that petitioned for extensions. However, unlike in many other countries, trans fat levels of less than 0.5 grams per serving can be listed as 0 grams trans fat on the food label. According to a study published in the Journal of Public Policy & Marketing, without an interpretive footnote or further information on recommended daily value, many consumers do not know how to interpret the meaning of trans fat content on the Nutrition Facts panel. Without specific prior knowledge about trans fat and its negative health effects, consumers, including those at risk for heart disease, may misinterpret nutrient information provided on the panel. The FDA did not approve nutrient content claims such as "trans fat free" or "low trans fat", as they could not determine a "recommended daily value". In July 2023, the agency published notice of plans for a consumer study to evaluate the consumer understanding of such claims and perhaps consider regulation allowing their use on packaged foods. However, there is no requirement to list trans fats on institutional food packaging; thus bulk purchasers such as schools, hospitals, jails and cafeterias are unable to evaluate the trans fat content of commercial food items.

An example of trans fat provided by the FDA.

Critics of the plan, including FDA advisor Dr. Carlos Camargo, have expressed concern that the 0.5 gram per serving threshold is too high to refer to a food as free of trans fat. This is because a person eating many servings of a product, or eating multiple products over the course of the day may still consume a significant amount of trans fat.

The American Medical Association supports any state and federal efforts to ban the use of artificial trans fats in U.S. restaurants and bakeries.

The American Public Health Association adopted a new policy statement regarding trans fats in 2007. These new guidelines, entitled Restricting Trans Fatty Acids in the Food Supply, recommend that the government require nutrition facts labeling of trans fats on all commercial food products. They also urge federal, state, and local governments to ban and monitor use of trans fats in restaurants. Furthermore, the APHA recommends barring the sales and availability of foods containing significant amounts of trans fat in public facilities including universities, prisons, and day care facilities etc.

2015–2019 phaseout

In 2009, at the age of 94, University of Illinois professor Fred Kummerow, a trans fat researcher who had campaigned for decades for a federal ban on the substance, filed a petition with the FDA seeking elimination of artificial trans fats from the U.S. food supply. The FDA did not act on his petition for four years, and in 2013 Kummerow filed a lawsuit against the FDA and the U.S. Department of Health and Human Services, seeking to compel the FDA to respond to his petition and "to ban partially hydrogenated oils unless a complete administrative review finds new evidence for their safety." Kummerow's petition stated that "Artificial trans fat is a poisonous and deleterious substance, and the FDA has acknowledged the danger."

Three months after the suit was filed, on 7 November 2013, the FDA issued a preliminary determination that trans fats are not "generally recognized as safe", which was widely seen as a precursor to reclassifying trans fats as a "food additive," meaning they could not be used in foods without specific regulatory authorization. This would have the effect of virtually eliminating trans fats from the US food supply. The ruling was formally enacted on 16 June 2015, requiring that within three years no food prepared in the U.S. is allowed to include trans fats, unless approved by the FDA. The FDA specifically ruled that trans fat was not generally recognized as safe and "could no longer be added to food after 18 June 2018, unless a manufacturer could present convincing scientific evidence that a particular use was safe." Kummerow stated: "Science won out."

The ban is believed to prevent about 90,000 premature deaths annually. The FDA estimates the ban will cost the food industry $6.2 billion over 20 years as the industry reformulates products and substitutes new ingredients for trans fat. The benefits are estimated at $140 billion over 20 years mainly from lower health care spending.

The FDA agreed in May 2018 to give companies one more year to find other ingredients for enhancing product flavors or greasing industrial baking pans, effectively banning trans fats in the U.S. from May 2019 onwards. Also, while new products can no longer be made with trans fats, foods already on the shelves are given some time to cycle out of the market.

Food industry response

Manufacturer response

Palm oil, a natural oil extracted from the fruit of oil palm trees that is semi-solid at room temperature (15–25 degrees Celsius), can potentially serve as a substitute for partially hydrogenated fats in baking and processed food applications, although there is disagreement about whether replacing partially hydrogenated fats with palm oil confers any health benefits. A 2006 study supported by the National Institutes of Health and the USDA Agricultural Research Service concluded that palm oil is not a safe substitute for partially hydrogenated fats (trans fats) in the food industry, because palm oil results in adverse changes in the blood concentrations of LDL and apolipoprotein B just as trans fat does.

In May 2003, BanTransFats.com Inc., a U.S. non-profit corporation, filed a lawsuit against the food manufacturer Kraft Foods in an attempt to force Kraft to remove trans fats from the Oreo cookie. The lawsuit was withdrawn when Kraft agreed to work on ways to find a substitute for the trans fat in the Oreo.

The J.M. Smucker Company, then the American manufacturer of Crisco (the original partially hydrogenated vegetable shortening), in 2004 released a new formulation made from solid saturated palm oil cut with soybean oil and sunflower oil. This blend yielded an equivalent shortening much like the prior partially hydrogenated Crisco, and was labelled zero grams of trans fat per 1 tablespoon serving (as compared with 1.5 grams per tablespoon of original Crisco). As of 24 January 2007, Smucker claimed that all Crisco shortening products in the US have been reformulated to contain less than one gram of trans fat per serving while keeping saturated fat content less than butter. The separately marketed trans fat free version introduced in 2004 was discontinued.

On 22 May 2004, Unilever, the corporate descendant of Joseph Crosfield & Sons (the original producer of Wilhelm Normann's hydrogenation hardened oils) announced that they have eliminated trans fats from all their margarine products in Canada, including their flagship Becel brand.

Agribusiness giant Bunge Limited, through their Bunge Oils division, are now producing and marketing an NT product line of non-hydrogenated oils, margarines and shortenings, made from corn, canola, and soy oils.

Since 2003, Loders Croklaan, a wholly owned subsidiary of Malaysia's IOI Group has been providing trans fat free bakery and confectionery fats, made from palm oil, for giant food companies in the U.S. to make margarine.

Major users' response

Beginning around 2000, as the scientific evidence and public concern about trans fat increased, major American users of trans fat began to switch to safer alternatives. The process received a large boost in 2003 when the FDA announced it would require trans fat labeling on packaged food starting in 2006. Packaged food companies then faced the choice of either eliminating trans fat from their products, or having to declare the trans fat on their nutrition label. Lawsuits in the U.S. against trans fat users also encouraged its removal.

Major American fast food chains including McDonald's, Burger King, KFC and Wendy's reduced and then removed partially hydrogenated oils (containing artificial trans fats) by 2009. This was a major step toward trans fat removal, as french fries were one of the largest sources of trans fat in the American diet, with a large fries typically having about 6 grams of trans fat until around 2007.

Two other events were important in the removal of trans fat. First, in 2013 the FDA announced it planned to completely ban artificial trans fat in the form of partially hydrogenated oil. Second, soon after this, Walmart informed its suppliers they needed to remove trans fat by 2015 if they wanted to continue to sell their products at its stores. As Walmart is the largest brick-and-mortar retailer in the U.S., mainstream food brands had little choice but to comply.

These reformulations can be partly attributed to 2006 Center for Science in the Public Interest class action complaints, and to New York's restaurant trans fat ban, with companies such as McDonald's stating they would not be selling a unique product just for New York customers but would implement a nationwide or worldwide change.