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Some key scientific studies and work of many medical researchers that established the health benefits of plant based whole food diet and lifestyle are elaborated here

Raw vegan study

The purpose of the study was to determine the effect of a very–high-fiber vegetable, fruit, and nut diet on serum lipids. Ten healthy volunteers took 3 different diets of 2 weeks duration. The diets were:

  1. 1. Raw vegan -  high vegetable, fruit, and nut (very–high-fiber) (formerly agricultural diet).

  2. 2. Starch - based containing cereals and legumes (early agricultural diet).

  3. 3. Low-fat (currently American healthy diet).

The results showed that the raw vegan high-fiber vegetable diet resulted in significant 33% reduction in low-density lipoprotein (LDL) cholesterol with lesser problem of constipation within 1 week and less constipated problems as compared to the starch-based and low-fat diets. [35].

Fresh vegetables and fruits study

In this study, 4,335 men and 6,435 women were recruited and followed-up until death (mean -16 years) to examine the association of dietary factors with mortality from ischaemic heart disease. The results showed that daily consumption of raw salad was associated with a 26% reduction in mortality from ischaemic heart disease, slightly greater than that for fresh fruit (24%)[36].

Flavonoid study

The researchers examined the association between 152-item flavonoid-containing foods and cardiovascular disease (CVD) mortality among participants in a large, prospective US cohort by 7 years follow-up. The result showed that participants who consumed large amounts of flavonoid-rich foods - such as anthocyanidins, flavan-3-ols, flavones, flavonols, and proanthocyanidins - were individually associated with lower risk of fatal CVD compared with those who consumed small amounts of flavonoid-rich foods [37].

Flavonoids are a diverse group of phytonutrients (plant chemicals). They are the most important  plant pigments and best known for their antioxidant action. Flavonoids found in almost all fruits and vegetables but flavonoid-rich foods include
(1) various fruits such as oranges, lemons, apples, pears, plums
(2) berries such as blackberries, strawberries, mulberries, red grapes
(3) nuts and beans
(4) various vegetables such as tomatoes, eggplants, onions, garlics, green leafy vegetables, corianders, broccoli, purple cabbages, sweet potatoes
(5) all herbs and spices especially turmeric and chili peppers
(6) beverages such as all types of tea including white tea, green tea and red wine.

Nuts and cardiovascular health study

Nut is a fruit composed of a hard shell and a seed such as macadamias, almonds, cashews, walnutspeanuts and pistachio. Nuts are natural foods rich in unsaturated fatty acids. Most nuts contain substantial amounts of MUFA (monounsaturated fatty acids), while walnuts are especially rich in both n-6 and n-3 PUFA (polyunsaturated fatty acids). In epidemiological studies found that healthy fats in nuts contribute to the beneficial effects of frequent nut intake (prevention of coronary heart disease, diabetes, and sudden death) and also beneficial effects of intake of nuts for short-term.(cholesterol lowering, LDL resistance to oxidation, and improved endothelial function) [38].

Three large cohort studies followed 71,764 US residents of African and European descent, primarily of low socioeconomic status and found that nut consumption was associated with decreased overall and cardiovascular disease mortality. According to the Nurses’ Health Study conducted at the Harvard University, over 10,000 nurses were followed-up over 35 years and the investigators found that people who ate nuts and seeds every day lived longer, healthier lives than people who did not eat nuts and seeds. The Adventist Health Study, another large prospective cohort study, following 34,000 the Seventh-day Adventists found that people who ate nuts and seedsfrequently lived longer and decreased all-cause mortality compared with those who did not eat nuts and seeds. There are at least 77 studies which concluded nut consumption was beneficial for health.

A fear that nuts consumption may lead to unwanted increase body weight, is misleading. Large published epidemiological studies were reviewed and concluded that adding nuts to the usual diet did not adversely affect body weight [40].

A major mechanism of animal-based diet causing increased risk of cardiovascular disease, is that animal based diet - meat, dairy products, eggs, and fish contains saturated fatty acids which lead to high blood cholesterol associated with cardiovascular disease.

Another mechanism from animal models researches is that meat contains choline. Choline is metabolized to trimethylamine-N-oxide (TMAO) by intestinal microbes which promote atherosclerosis. A study published in The New England Journal of Medicine investigated healthy participants who took two hard-boiled eggs and deuterium [d9]-labeled phosphatidylcholine before and after the suppression of intestinal microbiota with oral broad-spectrum antibiotics. The researchers demonstrated that plasma level of TMAO increased before the suppression of intestinal microbiota and TMAO decreased after the suppression of intestinal microbiota.

Moreover, the researcher followed-up participants continuously for 3 years about clinical outcomes. The results showed that participants who had higher baseline levels of TMAO had major adverse cardiovascular events. They concluded that intestinal microbes participate in phosphatidylcholine metabolism to form circulating TMAO which increased risk of incident major adverse cardiovascular events in human [41].

Hypertension is a global disease burden. A large famous study named Global Burden of Disease (GBD) analyzed independent effects of 67 risk factors and clusters of risk factors for people from 21 regions in 52 countries by over 500 researchers, followed for 20 years under Bill Gates Foundation. They found that one of three leading risk factors for global disease burden was high blood pressure.

In addition, they found that dietary risk factors and physical inactivity were the leading risk factors for global disease burden, with the most prominent dietary risks being diets low in fruits and those high in sodium. The major factor for most beneficial effects on health was that they changed to take plant-based diet including whole grains, legumes, and nuts consumption[42].

The knowledge of animal-derived protein affecting blood pressure was discovered by Dr. Arthur N. Donaldson since 1926. The vegetarian medical students were selected and were fed on animal-derived dietary protein. The results from blood pressure and blood test showed that their blood pressure and the activities of the body’s organs related to adrenal hormones increased [43].

According to an epidemiological study, the researchers found that consumption of vegetarian diets was associated with lower blood pressure[44].

In that era, there were no as many drugs as present. Dr. Walter Kempner reported the success from hypertension and chronic kidney disease treatment with boiled rice and fruit consumption and no meat consumption in Americans[45].

Later, there were many randomized controlled trials obviously proving an inverse relationship between animal protein and blood pressure. Eating plant protein substitute for animal protein can reduce blood pressure. A famous research namely PREMIER trial [46]. followed 810 participants with hypertension. Participants were divided to 2 groups, a meat protein intake group and a plant protein intake group. The results showed no change in blood pressure from baseline in meat protein intake group but in those who ate plant diet, high vegetables, fruits, legumes, and nuts intake had blood pressure as lower as antihypertensive medications taken.

Perception that blood pressure increases according to age is not correct. Indeed blood pressure is constant throughout our life but it is changed due to incorrect diets and lifestyles. The study of the Yanomami Indians called INTERSALT study, 10,079 males and females in 32 countries in Africa, South and North America, Asia, and Europe were studied. The Yanomami Indians had an active lifestyle (walk in the forest) with plant-based diet intake and no alcohol ingestion. The results revealed mean blood pressure levels of 95/61 mmHg, absence of blood pressure with increasing age. They had a very low urinary sodium excretion (0.9 mmol/24h) and high urinary potassium excretion. These results indicated that those who had a lower the urinary sodium excretion and a higher urinary potassium excretion had a lower the blood pressure [47].

A meta-analysis of randomized controlled trials estimating the effect of fiber supplementation on the prevention of hypertension had shown an inverse relationship between fiber intake and blood pressure. This indicated that people who had higher intake of fiber and whole grain, had lower blood pressure[48].

According to a randomized controlled trial, a high level of evidence, participants were divided into 2 groups; a whole-wheat foods group and a refined cereals foods group (wheat and oat flour) with 3 servings of their foods daily for 12 weeks. The results showed that the systolic blood pressure was significantly reduced by 6 mm Hg in the whole-grain foods group compared with a refined cereals foods group [49].

In a cross sectional study, cardio metabolic risk factors (blood pressure, plasma lipids, glucose, C-reactive protein-inflammatory marker) were evaluated in 3 groups of similar age subjects,
(1) subjects who had been on a low-calorie low-protein raw vegan diet for 4.4 years,
(2) endurance runners consuming Western diets, and
(3) sedentary subjects consuming Western diets. The results showed that subjects eating a low-calorie low-protein vegan diet and sedentary lifestyle had lowest blood pressure values, followed by endurance runners who were consuming a Western diet and non-obese sedentary subjects who were consuming typical Western diet, respectively. Plasma concentrations of lipids, glucose, C-reactive protein were highest in sedentary subjects consuming Western diets [50].

Among plant-based foods, some kind of foods reduced blood pressure outstandingly. A randomized controlled trial was conducted in patients who ingested a variety of foods (bagels, muffins, bars, buns, pasta, tea biscuits) that contained 30 g of milled flaxseed or placebo each day for over 6 months. Subjects could not easily identify if the food contained the flaxseed or not. The results showed that plasma levels of the ω-3 fatty acid α-linolenic acid and enterolignans increased 2- to 50-fold in the flaxseed-fed group but did not increase significantly in the placebo group. Systolic blood pressure was ≈10 mmHg lower in the flaxseed group compared with placebo. Patients who entered the trial with a systolic blood pressure ≥140 mmHg at baseline obtained a significant reduction of 15 mmHg in systolic blood pressure. The researchers concluded that the most potent antihypertensive effects correlated with circulating α-linolenic acid levels and lignan levels (molecular compound in flaxseed)[51].

A research funded by the British Heart Foundation, followed patients with hypertension by assigning with either dietary nitrate (250 mL daily, as beetroot juice) or a placebo (250 mL daily, as nitrate-free beetroot juice) for 4 weeks, after a 2-week run-in period and followed by a 2-week washout. The results showed that mean reduction systolic blood pressure was 7.7 mmHg if measured at clinic and in 8.1 mmHg if measured at home in beetroot juice group. Endothelial function improved by ≈20%, and arterial stiffness was reduced after dietary nitrate consumption with no change after placebo. The researchers concluded that based on intake of nitrate-rich vegetables such as beetroot juice might prove to be both an affordable, readily-available, and adjunctive treatment for a public health approach to hypertension and should be intervention before using antihypertensive medications [52].

Cooked vegetables consumption reduced slightly the antihypertensive effects of plant-based diet. The International Study of Macro/Micronutrients and Blood Pressure (INTERMAP) assessed the relation of blood pressure to consumption of raw and cooked vegetables. The results showed that estimated average systolic blood pressure was lower in raw vegetables consumption group than cooked vegetables consumption group (-1.9mmHg versus -1.3mmHg). Among commonly consumed individual raw vegetables, tomatoes, carrots, and scallions were the most common to reduce blood pressure. Among commonly eaten cooked vegetables, tomatoes, peas, celery and scallions were the most common to reduce the blood pressure.[53].

In addition to animal and animal-derived products, salty food is another cause of hypertension. This knowledge is from the research investigating from the postprandial effect of dietary salt on endothelial function. Normally endothelium releases nitric oxide, is a soluble gas which causes arterial dilatation,called endothelium-dependent dilation (EDD) in Medical language. Endothelial function is measured by intravascular ultrasound after infusions of vasoactive agents such as acetylcholine which stimulates nitric oxide production. If arteries dilate well that means endothelial function is good. In a randomized crossover study which followed normotensive healthy participants after receiving a meal with added salt (65 mmol Na, or 3.8g salt), which reflects the typical amount of salt consumed in a commonly eaten meal, and a control low-salt meal (5 mmol Na, or 0.3g salt) for 4 weeks. Endothelial function was measured at fasting and postprandial at 30 and 60 minutes. The researchers found that a high salt meal caused artery to shrink and reduction of artery flow to half compared with a low-salt meal at 30 and 60 minutes[54].

According to an observational follow-up study, trial of hypertension prevention (TOHP), adults with prehypertension were randomized to a sodium reduction intervention or control. The researchers found that in addition, sodium reduction led to a lower blood pressure, sodium reduction may also reduce risk of cardiovascular outcomes in 10 to 15 years after the trial[55].  

Dr. Neal D. Barnard, an endocrinologist, studied 99 individuals with type 2 diabetes who had intention to stop hypoglycemic medications, in a randomized control trial. Participants were randomly assigned to a diet following the American Diabetes Association (ADA) guidelines which included meat and animal-derived products or a low-fat vegan diet with very low fat and no meat and were followed up for 6 months. The results showed that 43% of the vegan group participants reduced diabetes medications, mean body weight decreased by 6.5 kg, mean HbA1c (A1C) fell by 1.23 points, and mean LDL cholesterol fell by 21.2%. These results indicated that these improvements were greater than the ADA group. Twenty-six percent of the ADA group participants reduced diabetes medications, mean body weight decreased by 3.1 kg, mean A1C fell by 0.38 points, and mean LDL cholesterol fell by 9.3%.

This study was a high level of evidence confirming that a very low-fat plant-based diet reverses diabetes and almost half of diabetic patients stopped all hypoglycemic medications within 6 months [56].

Normally people misunderstand about increase in blood glucose due to high fruits consumption. There were many researchers studying this issue and providing similar conclusions that high fruits intake either sweetened fruit or unsweetened fruit was not associated with blood glucose but high sugar intake from soft drink caused blood sugar shoot.

A high level of evidence research studied patients with newly diagnosed type 2 diabetes. Participants were randomized to one of two interventions; advice to consume at least two pieces of fruit a day neither amount limitation nor sweetened/unsweetened fruit (high-fruit) or advice to consume no more than two pieces of fruit a day (low-fruit). HbA1c (A1C) was measured at baseline and at 12 weeks follow-up. The results showed that HbA1c decreased in both groups with no difference between the groups [57].

According to the results from three prospective longitudinal cohort studies, the researchers of Harvard Medical School followed ≈ 200,000 individuals who were free of major chronic diseases at baseline but 12,198 participants developed type 2 diabetes during years of follow-up. When they analyzed the relationship between fruit consumption and risk of type 2 diabetes, they found that greater consumption of specific whole fruits, particularly blueberries, grapes, and apples, was significantly associated with a lower risk of type 2 diabetes, whereas greater consumption of fruit juice was associated with a higher risk [58].

Consumption of dates, despite their high sugar content (80% by weight) which is natural sugar and not like extracted to white sugar, demonstrated that it did not worsen serum glucose. Ten healthy subjects consumed, 100 g/day of either Medjool or Hallawi dates for a period of 4 weeks and their blood were recorded at baseline and week 4. The results showed that fasting serum glucose and triglycerides levels were not increased after consumption of both types of dates and serum triglycerides levels even significantly decreased by 8 or 15% after Medjool or Hallawi date consumption, respectively. The date consumption did not significantly affect the subjects’ body mass index (BMI), their serum LDL cholesterol, or HDL cholesterol levels. Serum activity of antioxidant enzyme significantly increased and serum oxidative status was significantly decreased by 33%, as compared to the levels observed before date consumption. Thus the researchers suggested that date can be considered an anti-atherogenic nutrient [59].

From all of these studies, I recommend that individuals with type 2 diabetes should not restrict fruits consumption. In contrast, they should consume sufficient amount of natural fruits but they should avoid fruit juice consumption especially ready-to-drink fruit juice packet, usually with added sugar. Besides, they should avoid desserts with added white sugar.

 How plant-based diet reverse diabetes

Unhealthy diet causes diabetes. Mechanism of diabetes development is acceleration of insulin secretion stimulated by unhealthy diet. If insulin release is stimulated for long-term until pancreatic cells become less sensitive to its effect, then it is called insulin resistance, which leads to develop type 2 diabetes. The function of insulin is to allow other cells to transform glucose into energy throughout the body and also helps the liver, muscle, and fat cells to store the glucose which you don’t need right away, so it can be used for energy later. To test if vegan diet or omnivore diet were different of this mechanism, a study [60] at Imperial College School of Medicine, London investigated 21 subjects who had been following a vegan diet and high carbohydrate intake for a minimum of 3 years prior to participating in the study and 21 subjects who were omnivores and low carbohydrate consumption. The subjects were matched for gender, age and body mass index (BMI). There was no difference in exercise activity and calories intake, just differed about sources of diets. Seven-day prospective food diaries were collected from the subjects. Insulin sensitivity was determined to assess insulin concentrations and intramyocellular lipid (IMCL) storage was determined to assess fat content in their muscle by biopsy at baseline and at the end of the study. The results showed that vegans had lower insulin concentrations and a significantly lower intramyocellular lipid (IMCL) storage compared with omnivores. These results had a tendency to indicate that plant-based diet or carbohydrate did not stimulate insulin secretion but animal diet or fat stimulated insulin secretion led to diabetes.

There are studies confirming that plant-based diet reduced of diabetes development. A sect of Christians used the Daniel Fast, a method of fasting based on the Biblical Book of Daniel. The book of the Biblical story told that Daniel and his friends were captive in prison and were offered "royal foods" including meat and wine by the king Daniel and his friends refused to eat foods forbidden by God, and instead asked for whole grains, fruits, vegetables, pulses, nuts, seeds, and water. At the end of the 10 days, the guard was surprised to see their good personal appearance and physical and mental health, compared with those who had indulged in the royal foods. The Daniel Fast research [61]involved a 21 day of libitum food intake period of specific foods, fruits, vegetables, whole grains, legumes, nuts, and seeds; however, excluding all meat and animal products including fish and junk foods. Forty-three subjects’ blood samples were examined. The results showed that the following parameters were lower following the fast as compared to before the fast: total cholesterol, LDL-cholesterol, blood glucose, insulin, and C-reactive protein (inflammatory marker).

[62].. Over 6-8 years follow-up in 1,065 participants with CKD found that participants who ate protein from animal sources had 59.4% deaths, while participants who ate protein from plant sources had 11.1% deaths. After adjustment for confounding factors such as age, smoking, alcohol use, underlying diseases, body mass index, physical inactivity and calories intake, results showed greater difference in mortality between the groups. These results indicated that the diet with higher proportion of protein from plant sources was associated with lower mortality in patients with CKD.

A fear of Nephrologist for protein from plant sources especially beans causes phosphorus or phosphate retention in the body of patients with CKD if they consume high plant protein is baseless with no supporting scientific evidence. It was evident from the research published in Clinical Journal of the American Society of Nephrology [63]. In a randomized, crossover trial in patients with CKD initially received two diets- either plant or meat based protein diet and then switching on to alternate diet. Their urine and blood samples were frequently monitored. The results showed that despite equivalent protein in the diets, subjects had lower serum phosphorus levels, and a trend towards decreased urine 24-hour phosphorus excretion in the vegetarian diet compared with the meat-based diet. The researchers presumed that these results are caused by plant protein in the form of phytate, which is not absorbed by most mammals. After laboratory analysis of phosphate-to-protein ratios for plant-based diet compared with meat-based diet, they found that the plant-based diet had a lower phosphate-to-protein ratio compared with meat-based diets. Therefore, protein from plant sources may theoretically lead to decreased phosphorus absorption compared with protein from animal.

The associations of diet with albuminuria and decline in estimated glomerular filtration rate (eGFR) were investigated by researchers at Harvard Medical School. They followed up 3,348 women with CKD and found that women who ate two or more servings of red meat (unprocessed mammalian muscle meat) per week were directly associated with higher microalbuminuria and eGFR decline. Meanwhile, women who ate plant foods and β-carotene rich foods were associated with lower microalbuminuria and eGFR decline [64].

Metabolic acidosis accelerates loss of kidney function in patients with progressive CKD. Animal protein is acidogenic diet but most fruits and vegetables are net-base producing foods. A research experimented in patients with CKD by receiving daily oral sodium bicarbonate. The researchers reported that oral sodium bicarbonate decreased kidney injury and eGFR decline. Another research comparing the efficacy of alkali-inducing fruits and vegetables with oral sodium bicarbonate to diminish kidney injury in patients with hypertensive nephropathy found that there was no difference in the effectiveness to diminish kidney injury in both groups but a fruits and vegetables group reduced blood pressure by half compared with an oral sodium bicarbonate group.

In a crossover study patients with type 2 diabetes and nephropathy,were provided either isolated soy protein or casein in random order. The findingindicated that isolated soy protein consumption improved urinary albumin excretion and several markers that may be beneficial for type 2 diabetic patients with nephropathy [65].

The lifetime prevalence of kidney stones is around 10% and incidence rates have been increasing every year along with age. In 303 participants of the Oxford arm of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort attended hospital with a new kidney stone episode. After analysis of the association of dietary intake of specific food groups and the risk of kidney stones, the researchers found that fresh fruit intake was inversely associated with risk of kidney stones. In contrast, there were significant positive relationship between intake of total meat and meat products and risk of kidney stones. Nutrient intake analysis showed that high intake of fresh fruits, fiber from whole grains, and magnesium were associated with a significant decrease in the risk of developing kidney stones while high intake of zinc was associated with a significant increased kidney stone risk [66].

Another study comparing the effect of two diets on kidney stone formation in patients by adhering either a diet with decreasing amounts of animal protein (52 g per day) and salt or a low-calcium diet with ad libitum animal meat consumption reported that kidney stone formation was lower in patients on low-animal-protein and low salt diet. Therefore, restriction of animal protein intake and salt provided kidney stone formation protection.

The study on uric acid stone formation evaluated volunteers by adhering 4 different diets; omnivorous diet, the Western type diet, ovo-lacto-vegetarian diet, or vegetarian diet. After analysis of uric acid crystallization to assess the risk of uric acid stone formation, the results indicated that the intake of a vegetarian diet resulted in the lowest risk of uric acid crystallization compared with the omnivorous diets which has highest risk of uric acid crystallization.

The Women’s Health Initiative (WHI) Observational Study was a prospective study investigating the health of postmenopausal women. The investigations revealed that higher intake of fiber, fruits, and vegetables were associated with a decreased risk of incident kidney stone formation in postmenopausal women [67].

In 2015, the World Health Organization (WHO) established an International Agency for Research on Cancer (IARC) to evaluate the carcinogenicity of the consumption of red meat referred to unprocessed mammalian muscle meat and processed meat such as hot dogs, bacons, and ham. These assessments were published in October, 2015. There were 2 major issues as follows;

1. Processed meat such as hot dogs, bacons, and ham is classified as “carcinogenic to humans” (Group 1) placed in the same category as tobacco smoking. This classification is based on sufficient evidence from epidemiological studies showing the development of cancer at least colorectal cancer in exposed humans.

Processed meat refers to meat that has been transformed through salting, curing, fermentation, smoking, or other processes to enhance flavor or improve preservation. One of the major causes contributing carcinogenic chemicals formation is preservatives containing nitrite compound. If any safe meat is preserved such as chicken nuggets, ham, or turkey, it would be assumed as a carcinogen [68].

2. Red meat such as beef and pork is classified as “carcinogenic to humans” (Group 2A). Red meat refers to all types of mammalian muscle meat including pork, beef, goat meat, and lamb containing heme iron for oxygen transportation.

There are many epidemiological studies showing a positive association between meat consumption and cancer. For example, the research about cooking meat[69] found that high-temperature cooking by panfrying, grilling, or barbecuing generally produced the highest amounts of carcinogenic chemicals named heterocyclic amines (HCAs).

The prospective study [70] in 29,361 men found that a high intake of meat was positively associated with prostate cancer risk.

A population-based, case-control study [71] in postmenopausal women found that consumption of the most grilled or barbecued and smoked meats over the life course increased risk of postmenopausal breast cancer.

The study [72] of the breast tissue of women undergoing reduction mammoplasty to examine the association of meat consumption by different cooking methods with breast tissue change found strong correlations of high consumption of fried meat and processed meat (sausages, bacons, ham) with changing in breast tissue of women (precancerous).

A prospective study of health care professionals’ health at Harvard School of Public Health [73] found that men with prostate cancer who had high intake of poultry, had a 4-fold increased risk of recurrence or progression compared with men who had low poultry intake. In addition, they found that their malignant prostate cells had higher choline (found naturally in eggs) concentrations than healthy cells.

An in-vitro study [74] suggested that the reduced intake of dietary methionine – an amino acid, rich in eggs- may be responsible for the decrease in mitochondrial damage from oxidation leading to decrease in cancerous cells in a Petri dish without affecting normal cells.

The largest cohort study [75] in workers who have been working for poultry slaughterhouse provided evidence that a human group with high exposure to poultry viruses had 9-fold increased risk of cancer of the penis compared with general population. This finding indicated that carcinogens might come from exposure to meat.

The National Institutes of Health (NIH)-AARP Diet and Health Study in 308,736 men and 216,737 women who completed a 124-item food frequency questionnaire for over an average follow-up of 6.3 years found that there were strongly positive associations betweendietary fat of animal origin and pancreatic cancer [76].

In the NIH-AARP Diet and Health Study, the investigators followed 491,841 participants to investigate intake of nitrate which is a naturally occurring compound in plants and nitrite which is found in several foods, especially processed meats, from dietary sources. The results showed that nitrite intake from animal sources had an increased risk of total renal cell carcinomas (RCC) but there was no association between RCC and nitrate intake from plant sources [77].

The study evaluating the relationship between food intake and testicular and prostatic cancers incidence in Japanese men for 50 years follow-up found that the death rate of testicular and prostatic cancer has risen 25-fold almost linearly during the last 48 years from 1947–95. Japanese lifestyle underwent drastic changes after the end of the Pacific War (1945). Most conspicuous was the change in dietary practices. The intake of milk and dairy products, meat and eggs increased 20, 9 and 7-fold, respectively, during the 48 years between 1950 and 1998. The researchers noted that the increased death from this cancer might be associated with the increased consumption of milk and dairy products because they contain saturated fatty acid and estrogen [78].

In an in-vitro study, cows milk was tested for their effects on the growth of cultures of prostate and breast cancer cells. The results showed that cows’ milk stimulated the growth of prostate cancer cells [79].

The first mechanism is total cholesterol, found in all meat but it is not found in all plant, and it is associated with the risk of cancers. In a large prospective study, almost 1.2 million Korean adults were enrolled in the National Health Insurance Corporation to examine the association between total cholesterol and site-specific and all-cancer incidence. The researchers found that high total cholesterol was positively associated with the risk of several different cancers [80].

- The second mechanism is heme iron, found in mammalian muscle meat, which is associated with the incidence of several different cancers including colorectal cancer [81]. Heme iron may promote the formation of endogenous N-nitroso compounds (NOCs), which have carcinogenic properties contributing to colorectal carcinogenesis. The study [82] in healthy male volunteers to investigate levels of fecal NOC found that those who had a higher heme iron supplement had a greater increased fecal NOC but there was not significantly greater with an equivalent amount of vegetable protein. Another study [83] investigating levels of fecal NOC after red meat consumption compared with fish consumption found that fecal NOC increased in healthy volunteers who ate red meat but fecal NOC decreased in those who ate fish.

- The third mechanism is insulin-like growth factor 1 (IGF-1), a hormone that plays an important role in childhood and adolescence growth. IGF-1 acts as growth factors by enhancing cell proliferation in a Petri dish. Too much IGF-1 leads to acromegaly and early death with either cancers or heart failure.

There is a process of programmed cell death that occurs in multicellular organisms called apoptosis. Apoptosis can occur automatically when cells are injured or damaged. Unfortunately, apoptosis cannot occur in tumor cell as it causes cell proliferations rapidly because damaged cell doesn’t not kill itself, on the other hand, it divides itself. An in-vitro study found that IGF-1 had anti-apoptosis of tumor cell property [84]. Animal protein especially in cow’s milk has been contaminated with excess IGF-1 levels resulting from the injection of cows with recombinant bovine growth hormone (rBGH) to increase milk yields, also beef and cow’s milk is contaminated by IGF-1. [85].

Many published results have shown an association between circulating IGF1 and breast-cancer risk. The pooled individual data analysis of 17 prospective studies [86] found that circulating IGF-1 was positively associated with breast-cancer risk, confined to oestrogen-receptor-positive tumours, and the association did not differ markedly by menopausal status either premenopausal or post-menopausal women.

IGF-1 is not associated with sex hormone (estrogen). Vegans had lower IGF-1 but higher sex hormone than meat-eaters. In contrast, meat-eaters had higher IGF-1 but lower sex hormone than vegans [87].

- The forth mechanism is roasting, grilling, barbecuing, or smoking. During these cooking steps -generate polycyclic aromatic hydrocarbons (PAHs) which are one of the best known classes of airborne carcinogenic pollutants. PAHs affect coke-oven worker, consumer, and all staff exposed to kitchen air. The epidemiological study revealed that PHA exposure was associated with an increased risk of some human cancers even though the back-door neighbors who live near the Chinese restaurant and usually inhale carcinogenic pollutants from meat cooking [88].

       There are a lot of scientific evidences supporting that plant-based diet decreased cancer risk and reversed cancer ranging from low level of evidences to high level of evidences. Below are some of the evidences-The epidemiological studies showing plant-based diet decreased cancer risk

The European Prospective Investigation into Cancer and Nutrition (EPIC) in over 400,000 participants for a mean follow-up of 8.7 years found that there were 1,613 of participants diagnosed with lung cancer. After dietary analysis, lung cancer risk was inversely associated with variety in fruit and vegetable consumption. These finding indicated that participants who had a higher variety in fruit and vegetable consumption had a lower lung cancer risk. The association was mainly driven by the effect in current smokers [89].

A prospective study in 1,490 women who were diagnosed for early-stage breast cancer for 2 years, found that those who reported eating a minimum of 5 vegetables-fruits servings daily, performing weekly physical activity equivalent to 30 minutes of walking at a moderate pace for 6 days a week, and maintaining their weight (not over or lower the standard of body mass index) were associated with decreased mortality rate compared with those who reported low vegetables-fruits intake, physical inactivity, and no weight maintenance [90].

A systematic review investigating the association between intake of dietary fiber and whole grains and risk of colorectal cancer, found that an intake of dietary fiberwas inversely associated with a reduced risk of colorectal cancer. These indicated that people who had a higher dietary fiber, in particular cereal fiber and whole grains intake had a lower incidence of colorectal cancer [91].

A population-based case–control study in Connecticut, New Jersey and western Washington State to examine the association between food group intake and subtypes of esophageal and gastric cancers, found that a higher intake of vegetables was associated with a decreased risk of both cancers while a higher intake of meats was associated with an increased risk of both cancers [92].

Turmeric treat cancers

Fifty year ago, curcumin, the yellow pigment in turmeric used for coloring and flavoring, is a natural anticancer compound from plant which is used in most research studies both in-vitro and in vivo. A number of laboratory studies on cancer cells have shown that curcumin has anticancer effects and it can kill stomach cancer, bowel cancer, urinary tract cancer, gynecological cancer, leukemia, lung cancer, thymus cancer, brain cancer, breast cancer, and bone cancer.

An up-to-date of over 50 studies, high level of evidence, which studied about benefits of curcumin in treating diseases. A clinical trial in 44 smokers with rectal aberrant crypt foci (ACF) on screening colonoscopy, with oral curcumin given daily, found that serum curcumin concentrations increased after oral curcumin was given. Participants underwent rectal endoscopies and tissue biopsies again and the result demonstrated that a short duration of curcumin treatment reduced ACF number [93]. Nowadays, the researchers have been exploring the combination of curcumin with chemotherapy in breast cancer patients [94], pancreatic cancer [95] , [96]. The researchers concluded the effectiveness of the combination in initial phase of experiment; however, the final conclusions have not been revealed because the experiments have not been finished yet.

In addition to the combination of curcumin with chemotherapy, the randomized controlled trial found that curcumin had a greater overall function of β-cells improvement than placebo in the prediabetic population [97]. Curcumin had a greater tenderness and swelling of joint reduction than placebo in patients with active rheumatoid arthritis (RA) [98].Curcumin decreased proteinuria in patients suffering from relapsing or refractory lupus nephritis [42].[100],decreased in total serum cholesterol [101], and reduced upper abdominal pain due to dysfunction of the biliary system [102].

If I have to choose and recommend you a natural food to eat daily, I would like you to choose turmeric based on scientific evidences. You can eat either spices in curry, rootstock, or powder by blending with fruits and vegetables. Tumeric dosage is 1 cc. or 1 grams per day which is enough and safe for long-term use because this dose is lower than Indians daily intake

Flaxseed and the result of research about human cancers

Flaxseed is one of the most important oilseed crops which have anti- cancers properties from in-vitro studies. These finding led to many studies about cancers treatment with flaxseed. A randomized controlled trial followed in postmenopausal patients with newly diagnosed breast cancer who were randomized to daily intake of either a 25 g flaxseed containing muffin or a control (placebo) muffin for 32 days. After tumor tissue biopsies, the results showed that daily intake of 25 g flaxseed could significantly reduce cell proliferation, increase apoptosis (apoptosis returned to work normally again) compared with before flaxseed eaten. Moreover, they found lignin containing in flaxseed in breast tissues greater than other normal tissues.

In addition to being one of the richest sources of lignin which has anticancer property, flaxseed provides oil rich in omega-3 and α-linolenic acid. It is an essential source of high quality protein and soluble fiber and has been considered as health promotion and disease prevention [103]. It should be eaten every day by using 1 tablespoon or 15 g ground flaxseed to the salad topping daily that may be enough.

The epidemiologic studies about anticancer property of plant-based diet

A multicenter case-control study of 1,369 patients with benign prostatic hyperplasia (BPH) and 1,451 controls showed that frequent users of both onion and garlic had a lower risk of BPH compared with nonusers or lower users [104].

A meta-analysis of studies on the association between cruciferous vegetables consumption and risk of renal cell carcinoma found that cruciferous vegetables consumption was related to the decreased risk of renal cell carcinoma [105].

In the Polyp Prevention Trial (PPT) trial–based cohort in participants with adenomatous polyp recurrence found that those who added normal food with high dry bean intake had a significantly reduced risk of advanced adenoma recurrence [106].

A randomized trial in China conducted on 75 patients who were identified by endoscopy to have dysplastic esophageal premalignant lesions to receive freeze-dried strawberry powder at 60 g/d for 6 months; the powder was mixed with water and drunk. After six months, the researchers assessed the changes in histologic grade of these lesions (primary endpoint) in a blinded fashion. The results demonstrated that participants who drank strawberry juice could reduce the histologic grade of dysplastic premalignant lesions 80.6% [107].

A clinical trial in men with prostate cancer and rising prostate-specific antigen (PSA) after surgery or radio therapy by treating with 240 ml of pomegranate juice daily to determine PSA progression found that PSA decreased 4-fold comparing pretreatment and antioxidant levels increased comparing pretreatment [108].

An epidemiological study concluded that phytochemicals in broccoli and other Cruciferous species appear most closely associated with reduced cancer risk in organs such as the colorectum, lung, prostate, and breast [109].

Epidemiological studies found that the Allium genus such as garlic, onions, shallots, leeks, and chives had association with a decreased risk of cancer, particularly cancers of the gastrointestinal tract. There are mechanistic studies indicating potential mechanisms of the anticancer activity of various Allium vegetable extracts [110].

Antiproliferative effects of plant-based diet

In vitro studies found that antioxidants in various fruits and vegetables have anti-proliferative effects in-vitro.

The comparative study to determine the antiproliferative activities of common fruits on human liver cancer cell growth found that cranberry showed the highest inhibitory effect, followed by lemon, apple, strawberry, red grape, banana, grapefruit, and peach and the last rank are pear, orange, and pineapple [111].

Antiproliferative activities of common vegetables were also studied, in-vitro, on human liver cancer cells. This study found that the different kind of vegetables affected differently antiproliferative activities. The allium genus such as onion and garlic showed the highest inhibitory effect, followed by the Cruciferous species such as broccoli, kale, cauliflower, and cabbage [112].

An in vitro study found that berries extracts including blueberry, cranberry, and strawberry inhibited growth and stimulate apoptosis of human cancer cells [113].

Another in-vitro study found that Brassica species (broccoli, cauliflower and Brussels sprouts) containing salforaphane had anti-proliferative and chemoprotective effects towards DNA oxidative damage [114].

The research of salforaphane properties in broccoli found that it is produced when the  myrosinaseenzyme  transforms glucoraphanin, a glucosinolate, into sulforaphane upon damage to the plant (such as from chewing or chopping), which allows the two compounds to mix and react. Sulforaphane which has anti-proliferative effects is heat stability but myrosinase which produced sulforaphane is markedly inactivated after heating. Therefore, cooking broccoli immediately after chopping caused a decline sulforaphane due to inactivated myrosinase. The solution is chopping broccoli then leave for 40 minutes before cooking. Leaving broccoli induces sulforaphane formation by myrosinase, so sulforaphane which is produced before cooking is stable because it is not damaged after heating.

In case of freezing broccoli, it is always preceded by a blanching step to inactivate enzymes that cause product deterioration. Therefore, chopping and leaving broccoli were useless because myrosinase was inactivated prior to freezing by blanching or some other heat treatment. The solution is adding ½ teaspoons powdered mustard seeds to cooked broccoli. Myrosinase in powdered mustard seeds significantly increased the formation of sulforaphane in the heat processed broccoli [115].

An in vitro experiment revealed that non-alcoholic, red seedless grape juice was effective in inhibiting the activity of human placental aromatase which plays an important role in promoting breast cancer growth [116].

Another in vitro study found that compounds isolated from pomegranate significantly inhibited breast cancer cell proliferation and anti-aromatase enzyme which plays a key role in breast carcinogenesis [117].

An in vitro study found that phytosterols in Riceberry bran showed strong anti-leukemic cell proliferation in a Petri dish [118].

In vitro study reported that anthocyanin-enriched sweet potato protected against colorectal cancer by inducing cell-cycle arrest, antiproliferative, and apoptotic mechanisms [119].

The research found that the sweet potato contains ranges of protein from 4% to 27% in leaves and 1% to 9% in roots. It is an excellent source of antioxidants and anticancer agent such as β-carotene and anthocyanin [120].The sweet potato is a staple food source for many indigenous populations in Africa and Okinawa Island where in an area people live the longest in the world. It is potential as valuable food for health promotion in the future. Moreover, the sweet potato is one of the crops selected for NASA's Advanced Life Support Program for potential long-duration lunar/Mars missions [121].

There was a randomized study assessing the difference between white, yellow, and purple potato cultivars. Healthy men were randomized to consume a total of 150 g per day of cooked potato for 6 weeks and their blood was collected. Potatoes were analyzed as well. The results showed that compared with the white potato group, the yellow potato group had higher concentrations of phenolic acids (antioxidants) and carotenoids, whereas the purple potato group had higher concentrations of phenolic acids and anthocyanins. Men who consumed yellow potato and purple potato tended to have lower plasma IL-6 (inflammatory cytokine) and 8-hydroxydeoxyguanosine (8-OHdG) (a marker of oxidative damage to DNA) concentration compared with those consuming white potato. The purple potato group tended to have a lower plasma C-reactive protein (CRP) (inflammatory biomarker) concentration than the white potato group. The researchers concluded that yellow potato and purple potato consumption reduced inflammation and DNA damage rather than the white potato consumption

Animal-based diet worsen gout compared with plant-based diet

Normal blood uric acid level is neither too high nor too low. A study conducted in Taiwan included 354,110 subjects without a history of gout. There were 33,562 all-cause deaths during the study period. After the researchers assessed the associations between serum uric acid level and mortality, they found that individuals with serum uric acid levels at either extremes are at higher risk for all-cause mortality. Serum uric acid levels of 0.30-0.41 mmol/l (5-7 mg/dl) were associated with the lowest mortality rate and should be regarded as optimal [127].

Up-to-date, there is at least one study [128], a high level of evidence, indicating what kind of foods can reduce uric acid concentration, published in Arthritis & Rheumatology. The study was conducted on 103 adults with pre- or stage 1 hypertension. Participants were randomly assigned to receive either the Dietary Approaches To Stop Hypertension (DASH) diet, emphasizing fruits, vegetables, whole grains, nuts and low-fat dairy foods with a low intake of red meats, sweets, and saturated fats, or a control diet (typical of the average American diet). The results showed that the DASH diet lowered serum uric acid while there was no change in control group. Moreover, participants were further fed low, medium, and high sodium levels and the results showed that higher sodium intake decreased serum uric acid.

The research included 633 participants with gout. Participants were asked about daily intake of various purine-containing food items during the 2-day period prior to the gout attack. The results showed that acute purine intake increased the risk of recurrent gout attacks by almost 5-fold among gout patients. The impact from animal purine sources was substantially greater than that from plant purine sources by 2-fold [129]. These finding indicated that purine-rich foods from animal origin reduced the risk of gout attacks rather than purine from plant sources.

The traditional belief that milk contains calcium, phosphorus, and is fortified with vitamin D and all these ingredients may improve bone health and reduce fracture incidence is not correct. A meta-analysis of cohort studies in 195,102 women (3,574 hip fractures) and 75,149 men (195 hip fractures) to assess the association of milk intake with risk of hip fracture found that there was no overall association with total milk intake and hip fracture risk [130].

Moreover, two large Swedish cohorts which were published in British Medical Journal followed 61,433 women and 45,339 men (39-79 years at baseline) to observe fracture incidence. The results showed that high milk intake (three or more glasses of milk a day) was associated with higher mortality in one cohort of women and in another cohort of men, and with higher fracture incidence in women compared with low milk intake (less than one glass a day) [131].

The research following 2 groups of participants found that fruit, vegetable, and antioxidant consumption were significantly lower among individuals with depression than the comparison participants [132].

A cross-sectional study of Seventh-Day Adventists to examine associations between mood state as a result of adherence to a vegetarian or omnivorous diet by using Depression Anxiety Stress Scale (DASS) and Profile of Mood States (POMS) questionnaire found that participants with vegetarian diet had better mood and lower depression than those with omnivorous diet [133].

A cross-sectional study of 986 Japanese elderly to analyze the 75-item foods on depressive symptoms demonstrated that elderly who ate plant-based diet had lower depressive symptoms than those who ate omnivorous diet. Among kinds of vegetables, tomato-rich diet was independently related to lower prevalence of depressive symptoms [134].

A randomized controlled trial followed omnivores who consume both plant and meat. Participants were randomly assigned to (1) a control group consuming meat, fish, and poultry daily (OMN); (2) a group consuming fish 3-4 times weekly but avoiding meat and poultry (FISH), or (3) a vegetarian group avoiding meat, fish, and poultry (VEG) for 2 weeks. Participants completed the Profile of Mood States (POMS) and the Depression Anxiety and Stress Scales (DASS) questionnaires at baseline and after two weeks, the results showed that after the diet intervention, VEG participants reduced their arachidonic acid (AA) levels which were associated with depressive symptoms. Several mood scores for VEG participants improved significantly but mood scores were unchanged for OMN or FISH participants [135].

A meta-analysis of 21 studies analyzing the association between dietary patterns and depression found that high intakes of fruit, vegetables, fish, and whole grains were associated with a reduced depression risk [136].

A systematic review of 11 cross-sectional studies and epidemiological studies found that low folate, a nutrient from plant, status was associated with depression [137].

However, a randomized controlled trial was conducted in participants with increased familial risk of mood disorder. Participants were randomized to folic acid (2.5 mg daily) or identical placebo liquid. The results showed that the incidence of mood disorder in the folic acid and placebo groups had non-significant difference. This finding indicated that exertion to extract renewable natural food in this way does not work because the combination of over hundred thousand of nutrients from natural food cannot be compensated with a single nutrient extraction [138].

A systematic review and meta-analysis of studies about the association of dietary fiber and whole grain intake with the incidence of stroke found that total dietary fiber intake was inversely associated with risk of stroke; in the other words, greater dietary fiber and whole grain intake was associated with lower risk of stroke [139].

A meta-analysis of studies on association of fruits and vegetables consumption with the risk of stroke showed that fruits and vegetables consumption were inversely associated with the risk of stroke; in other words, greater fruits and vegetables consumption was associated with lower risk of stroke [140].

Pathological evidence indicated that atherosclerotic vascular disease as a contributing factor or a major factor to Alzheimer’s disease [141]. According to epidemiological studies, atherosclerotic vascular disease risk factors are the risk factors of developing Alzheimer’s disease as well.

In vitro study found that the generation of cerebral β-amyloid (Aβ), seems to be a key initiating event in Alzheimer’s disease, depends exclusively on the presence of cholesterol in the cells [142].

Moreover, the study found that serum cholesterol level was associated with elevated cerebral β-amyloid (Aβ) level [143].

The research about the association of vascular risk factors with Alzheimer’s disease development found that treatment of vascular risk factors was associated with a slower decline in Alzheimer’s disease incidence [144].

In epidemiologic study found that in a rural community in India where people rarely eat meat had the lowest incidence rates of Alzheimer’s disease [145].

While the prevalence of Alzheimer’s disease have risen in Japanese immigrating to Hawaii compared with Japanese living in Japan according to the nutrition transition after immigration [146].

The Adventist Health Study in the Seventh-Day Adventists who resided within the Loma Linda area found that the incidence of dementia have risen according to amount of meat consumption [147].

A cross-sectional study of 2,031 Norwegian elderly individuals to examine the relationship between intake of different plant foods and cognitive performance found that subjects with high intake of fruits, vegetables, grain products and mushrooms performed significantly better in cognitive tests than those with very low or no intake.

For individual plant foods, the positive cognitive associations of carrots, cruciferous vegetables, citrus fruits and high-fiber bread were most pronounced. The only negative cognitive association was with increased intake of white bread [148].

The research found that in Western Hemisphere countries, the apolipoprotein E (ApoE) ϵ4 carriers had higher levels of serum total cholesterol and blood pressure at midlife than noncarriers. Carrying the ApoE ϵ4 allele was a significant risk factor for Alzheimer disease at late-life [149].

The research in Nigerian blacks who have the highest observed frequency of the ApoE ϵ4 allele in world populations and eat plant-based diet found that no one was diagnosed to Alzheimer’s disease. This result showed that the dietary intake is more influential than genes [150].

The epidemiological study demonstrated that there are low incidence rate of Parkinson’s disease in smokers due to nicotine. Nicotine’s ability remains even though confounding factors such as caffeine consumption and hereditary Parkinson’s disease were eliminated [151].

The nightshade family (Solanaceae) such as tomatoes, potatoes, eggplants or aubergines, and peppers containing nicotine may reduce Parkinson’s disease risk.

In a population-based, study compared 490 patients with newly diagnosed with Parkinson’s disease, with normal population, found that individuals with Parkinson’s disease were associated with lower consumption of all edible Solanaceae compared with normal controls [152].

In a study in patients with Parkinson’s disease, participants were divided to 2 groups- a plant-based food group (no meat) and an omnivorous group and were followed up for 4 weeks. Comparisons of the outcomes between the two groups of patients were made using Mann–Whitney tests. The results showed that the plant-based food group showed a significant improvement in their motor performances compared with the omnivorous group.

A cross-sectional study to evaluate the body content of organochlorines (OC), pesticides (such as β-HCH, p,p’-DDE,p,p’-DDT, and PCB), in vegans, omnivores and fat-substituted by olestra group. The results showed that plasma concentrations of OC compounds were significantly lower in vegans and fat-substituted by olestra group compared with omnivores [153]; These finding indicated that OC compounds were absorbed into the body with animal-derived fat.

A meta-analysis study on dairy foods intake and Parkinson’s disease including 1,083 Parkinson’s disease cases among 304,193 subjects found that dairy foods, especially for milk and cheese, were associated with increased risk of Parkinson’s disease [154].

The Parkinson Research Examination of CEP 1347 Trial (PRECEPT) study determining the relationship between serum uric acid and rates of Pa