Harvard Meat Study

On Monday, March 12, 2012, the Archives of Internal Medicine published online "Red Meat Consumption and Mortality: Results From 2 Prospective Cohort Studies," a study done by researchers from the Harvard School of Public Health.  This study found that eating even one serving daily of red meat increased total mortality and risk of mortality from cardiovascular disease and cancer.

The researchers carefully controlled for intakes of total energy, whole grains, fruits, and vegetables; age; body mass index; race (white or nonwhite); smoking status; alcohol intake; physical activity level; multivitamin use; aspirin use; family history of diabetes mellitus, myocardial infarction, or cancer; and baseline history of diabetes mellitus, hypertension, or hypercholesterolemia. In women, they also adjusted the data for postmenopausal status and menopausal hormone use.

Some in the cattle industry have questioned the validity of the food frequency questionnaires used in this type of study (here).  The authors of the study responded:

"However, all the questionnaires used in this study have been validated against multiple-day food records—at least 14 days during a year—and have been found to be acceptable in terms of validation and reproducibility.

"Second, although there [are individual] day-to-day variations in food consumption, people are generally eating in a pattern that can be captured by the questionnaire. We were interested in between-person variation[s], and we were comparing people who eat a high amount of red meat to those who eat a low amount of red meat. Because we repeated the measurements every four years, the cumulative average used in the analysis represents a long-term dietary pattern. That is a strength of this study, because many other studies may have only a single measure at baseline.

"Last, but most importantly, the measurement error generally tends to attenuate the association, and if we corrected the measurement error using some statistical methods, the associations were much stronger!"  [emphasis added]

Some have responded to this by claiming that "correlation doesn't equal causation" (as if the Harvard researchers don't realize this), or that the results only apply to consumption of conventional meat, not grass-finished.

Such a response ignores two important facts:

1) This study is only one among hundreds finding an association between red meat consumption and increased mortality from heart disease and cancer. 

2) Basic research has shown that these hazards arise from components that occur in meat from grass-fed animals at levels equal to or greater than levels found in meat from grain-fed animals.  


The following provide examples of the large number of studies finding positive associations between consumption of red meat and adverse health outcomes:

Meat consumption and colorectal cancer risk: Dose-response meta-analysis of epidemiological studies

Meat consumption and risk of colorectal cancer:  A meta-analysis of prospective studies 

Processed meat consumption and stomach cancer risk meta-analysis


Meat consumption and the risk of type 2 diabetes meta-analysis


Meat consumption and prostate cancer risk


Thus, this new study is not some isolated, rare, unusual finding.  It resonates with a large body of corroborating epidemiological evidence finding a positive association between red meat consumption and risk of or mortality from disease.  It adds to that growing body of evidence. 


Of course, "correlation does not prove causation," so some scientists have taken the next step required, doing research to find out if there are any plausible mechanisms by which consumption of meat could increase the risk of mortality. 

So far, researchers have found that a number of components of red meat have biological effects providing plausible mechanisms by which diets rich in meat could increase the risk of chronic diseases and mortality.  The suspect components include animal protein, cholesterol, arachidonic acid, heme iron, and Neu5Cg sialic acid, all of which naturally occur in red meat.  Further, the concentration of these components of meat is not markedly affected by feeding or pharmaceutical strategy used in raising the animals; meat from grass-fattened animals has practically the same amount of these components as meat from grain-fattened animals.


Animal Protein


Animal protein typically forms a larger proportion of lean grass-fed than conventional fatty meat, and promotes increases in IGF-1 levels, which appears involved in promotion of breast, colon, and prostate cancers.

High animal protein intake raises serum IGF-1 levels. [Full text]

IGF-1 has roles in growth promotion and carcinogenesis. [Abstract]

Elevated IGF-1 levels were associated with a 49% increased risk of prostate cancer and a 65% increased risk of premenopausal breast cancer.  [Abstract]

Elevated IGF-1 levels are associated with increased risk of prostate cancer, lung cancer, colorectal cancer, and premenopausal breast cancer. [Abstract]  


Dietary Cholesterol

Starting with a zero cholesterol diet, adding small increments of dietary cholesterol raises serum cholesterol levels, in a dose-response fashion.[Full text]

Elevated serum cholesterol increases the risk for cardiovascular disease. [National Cholesterol Education Program]

Elevated serum cholesterol increases risk of ischemic stroke in the general Japanese population.[Abstract]

Mice fed a high fat, high cholesterol diet and showing elevated serum cholesterol have increased mammary tumor growth and metastases compared to controls. [Abstract]


Emerging evidence indicates that oxidized cholesterol plays an important role in the angiogenesis process that supports tumor growth. [Abstract]  

The more unnecessary LDL cholesterol in the blood, the more likely there will be oxidized cholesterol in the blood.

Individuals with elevated serum cholesterol found to have a 35% increased prostate cancer risk.[Abstract]

Cholesterol-depletion of breast and prostate cancer cell lines induces apoptosis  whereas cholesterol-enrichment via elevated serum cholesterol (due to diet) supports tumor growth and progression.[Abstract, Full Text]

Elevated LDL positively correlates with increased risk of advanced stage colon cancer.[Abstract]

Patients with colon adenomas, the precursors of colon cancer, have elevated LDL.[Abstract]

Patients with distant metastases of colorectal cancer have significantly elevated serum cholesterol levels compared to those without metastases. "Elevated serum lipid levels may facilitate the development of distant metastasis in CRC [colorectal cancer] patients."[Abstract] 

Heme Iron, Arachidonic Acid, HCAs, PHAs, and Neu5Gc

Heme iron, a form of iron found at the highest levels in red meats. I discussed some of the evidence linking iron intake and levels to inflammatory diseases (including heart disease and cancer) in this post.


Arachidonic acid, which occurs in meat from grass-fed animals at levels equal to or greater than found in meat from grain-fed animals, and is involved in cancer promotion, which I discussed in this post.

Neu5Gc, a type of sialic acid produced by non-human mammals but not by humans, which enters humans through consumption of mammalian meat and milk, is incorporated into epithelial and endothelial tissues, incites an auto-immune response and inflammation in those tissues, and has been found concentrated in malignant tumors (full text).  

Of interest, this paper on Neu5Gc includes the following passage:

"Although earlier studies claimed the absence of Neu5Gc from normal human tissues, we showed thatit is also present in smaller amounts in normal human epithelial and endothelial cells in vivo (Tangvoranuntakul et al. 2003). Furthermore, we recently demonstrated that mice with a human-likedefect in the CMAH gene had no detectable Neu5Gc (Hedlund et al. 2007), effectively ruling out an alternate mammalian pathway for synthesis. This paradox is explained by our finding that humans can metabolically incorporate Neu5Gc via oral intake (Tangvoranuntakul et al. 2003). We have therefore suggested that the well-known epidemiological association of human cancers with consumption of red meat and milk (which happen to be the richest dietary sources of Neu5Gc) (Rose et al. 1986; Norat et al. 2002; Lewin et al. 2006) might be related to this unusual metabolic accumulation. Here, we have demonstrated another required component for this hypothesis – circulating antibodies that can recognize Neu5Gc on human tissues and can potentially generate chronic inflammation. To our knowledge, this is the first example wherein a nonhuman molecule becomes metabolically and covalently incorporated onto human cell surfaces, even in the face of an immune response against it. Further studies are needed to firmly establish a link between Neu5Gc expression in tumors and anti-Neu5Gc in the pathogenesis of carcinomas."[emphasis added]

This passage illustrates that the epidemiological association of human cancers with consumption of red meat and milk is "well-known" among scientists and that they have moved beyond questioning the association (since it is scientifically well established) to elucidating the mechanisms responsible for this association, in this case Neu5Gc, the first nonhuman molecule proven to become part of human cell surfaces despite an immune response against it.


I first learned about Neu5Gc from this video by Plant Positive:

Cooking meat at high temperatures, particularly over open flames, produces heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) which are carcinogenic.   These will form in meat cooked at high temperatures regardless of how the source animal was fed.    The National Cancer Institute says "numerous epidemiologic studies have used detailed questionnaires to examine participants’ meat consumption and meat cooking methods to estimate HCA and PAH exposures. Researchers found that high consumption of well-done, fried, or barbecued meats was associated with increased risks of colorectal (14), pancreatic (15, 16), and prostate (17, 18) cancer."
Summary

Protein, cholesterol, iron, arachidonic acid, and Neu5Gc all occur naturally in meat, and HCAs and PAHs form in meat cooked at high temperatures, regardless of the feeding or pharmaceutical strategy used to raise the animals from which the meat is taken.  

The studies I cited above only provide a small sampling of the laboratory data providing evidence of plausible mechanisms by which an excessive consumption of meat could increase one's risk of mortality.  Epidemiological research generated both the lipid hypothesis and the hypothesis that red meat increases mortality risk, but we now have much stronger data to support these hypotheses. 

We have evidence for specific mechanisms by which these naturally occuring substances can initiate (HCAs or PAHs) or promote (protein, cholesterol, iron, arachidonic acid, and Neu5Gc) fatal diseases, so only someone ignoring or ignorant of the above data could argue that the association of increased risks of mortality from cancer and heart disease apply only to people eating meat from grain-fed or drug-treated animals, or that the epidemiological associations have no plausible physiological basis.

Arachidonic Acid and Breast, Prostate, and Colon Cancers

Arachidonic acid (AA) is a long-chain polyunsaturated omega-6 fat.  It does not occur in commonly consumed plant tissues, so animal foods supply dietary AA consumed by humans.  According to the National Cancer Institute, the top ten sources of arachidonic acid in U.S. diets include:

1. Chicken and chicken dishes (27%)
2. Eggs and egg dishes (18%)
3. Beef and beef dishes (7%)
4.  Sausage, franks, bacon, and ribs (7%)
5. Other fish and fish mixed dishes (6%)
6.  Burgers (5%)
7.  Cold cuts (3%)
8.  Pork and pork mixed dishes (3%)
9.  Mexican mixed dishes (3%)
10.  Pizza (3%)


Since AA is used in muscle cell membranes the AA (20:4 n-6) content (g/100 g edible) of lean flesh from grass-fed cattle may not differ significantly from the meat of corn-concentrate fed  cattle.  One study actually found that the highest AA level occurred in grazed (grass-fed) Scott cattle and the lowest level in Simmental cattle fed concentrate (corn) [1, full text]:

Both lean and fat from animals provides AA; lard may have the highest AA content of any animal fat: 

"The aim of this study was to accurately quantitate the AA content of visible fat and the lean portion of beef, lamb, pork, chicken, duck, and turkey. The visible fat of meat contained a significant quantity of AA, ranging from 20 to 180 mg/100 g fat, whereas the AA content of the lean portion of meat was lower, ranging from 30 to 99 mg/100 g lean meat. Beef and lamb meats contained lower levels of AA in both the visible fat and lean portion than that from the other species. The highest level of AA in lean meat was in duck (99 mg/100 g), whereas pork fat had the highest concentration for the visible fats (180 mg/100 g). The lean portions of beef and lamb contained the higher levels of n-3 polyunsaturated fatty acids (PUFA) compared with white meats which were high in AA and low in n-3 PUFA. The present data indicate that the visible meat fat can make a contribution to dietary intake of AA, particularly for consumers with high intakes of fat from pork or poultry meat." [2 ]

In the absence of AA intake, an intake of linoleic acid (LA, the omega-6 fat found in plants) up to four percent of calories either has no effect on AA or reduces AA levels, but an intake of twenty percent of calories might stimulate undesirable eicosanoid synthesis temporarily. [3, 4]  In one study, a liquid formula diet supplying twenty percent of calories as linoleic acid significantly reduced platelet aggregation (-25%) and thromboxane formation (-43%). Levels of some prostaglandin metabolites increased during the first 10 days, then declined to a level lower than the pre-experimental values at the end of the 3-week period. [4]  Thus, it appeared that a diet enriched in LA ultimately reduced tissue levels of AA metabolites.

A review of 36 high-quality reports of studies of the effect of dietary LA on AA levels found "Increasing LA by as much as 551% from baseline and reducing LA by as much as 90% from baseline failed to yield compelling evidence supporting the concept that any conversion of dietary LA to downstream metabolites results in tissue enrichment of AA, a notion commonly assumed." [26 full text]  

In contrast, increased dietary intake of AA (i.e. meat and animal fat) increases the production of pro-inflammatory eicosanoids in humans. [5, 6 ]

Probably the body regulates conversion of LA to AA according to need, the same way it regulates conversion of beta-carotene to retinol according to need.  Although it is possible to overdose on retinol (so-called vitamin A), humans can't get an overdose of retinol by route of eating carotenoids because the body will not convert carotenoids to retinol unless it has a retinol deficiency.  Similarly, it appears that the body does not convert LA to AA unless it has a deficiency of AA, but we can get an excess of AA by eating AA directly, just as we can get an excess of retinol by eating retinol directly.  This suggests that human metabolism is not well adapted to diets containing preformed retinol or AA.

 Cells supplied with exogenous AA show increased production of an eicosanoid, PGE2, which in turn decreases production of tumor necrosis factor (TNF), a type of cytokine that induces programmed cell death (apoptosis) in tumor cells. [7]   This becomes relevant to cancer promotion; less TNF means less immune system control over tumor cells.

Research seems to suggest that promotion of AA metabolism promotes breast, prostate, and colon cancer, while inhibition of AA metabolism, even using aspirin or other COX2 inhibitor NSAIDs, reduces occurrence of these, the most common cancers in the United States.

"Epidemiologic evidence suggests the incidence of breast, colon, and lung cancers is inversely related to the use of aspirin and nonsteroidal anti-inflammatory drugs, which are nonspecific inhibitors of COX. COX-1 and COX-2 are enzymes that generate prostaglandins and thromboxanes from free arachidonic acid." [8 ] 

Below I have quoted some relevant publications or abstracts (when I don't have access to the full document), showing that scientists doing basic research on the biochemistry involved in cancer growth have identified AA metabolism as a target for cancer prevention and therapy. 

If you search PubMed with "arachidonic acid and (insert name of cancer)" you will find many more like these.

Breast Cancer

"Arachidonic acid (AA) and its metabolites play critical role in the development of breast cancer, but the mechanisms through which AA promotes mammary tumorigenesis and progression are poorly understood." [9]

Arachidonic metabolism by LOX enzymes is involved in lymph node metastasis of breast cancer.  [10 full text ]

"Arachidonic acid, a dietary cis-polyunsaturated fatty acid, stimulates adhesion and migration of human cancer cells on the extracellular matrix by activation of intracellular signaling pathways."[11 full text ]

"In our previous work, we utilized a highly metastatic human [breast] cancer cell line, MDA-MB-435, and demonstrated that arachidonic acid induced cellular adhesion to collagen type IV in an integrin-dependent manner requiring the activation of multiple signal transduction proteins." [12 full text ]

"The estrogen independent MDA-MB-435 cell line has the advantage that it metastasizes consistently to the lungs and forms quantifiable secondary nodules when injected into the mammary fat pads. With these breast cancer cells, the stimulating effects of polyunsaturated omega-6 fatty acids on both primary tumor growth and metastasis were demonstrated; in contrast, the long-chain omega-3 fatty acids were inhibitory. The model can also be adapted to examine dietary fatty acids, and inhibitors of their metabolism, as experimental adjuvant therapy after surgical excision of the primary tumors. ..The results obtained by these several approaches have demonstrated distinct roles for the cyclooxygenase and lipoxygenase-mediated products of omega-6 fatty acid metabolism, and suggest new approaches to experimental breast cancer therapy. " [13 ]

"15(S)-Lipoxygenase-2 Mediates Arachidonic Acid-stimulated Adhesion of Human Breast Carcinoma Cells through the Activation of TAK1, MKK6, and p38 MAPK....The cis-polyunsaturated fatty acid arachidonic acid and its many metabolites are important mediators of cell signaling with roles in inflammation, platelet aggregation, tissue development, and carcinogenesis (1–5). The cis-polyunsaturated fatty acids have been implicated in a number of in vivo and in vitro rodent studies that link fat intake and cellular fatty acid levels with carcinogenesis, tumor development, and metastasis (6–8)."  [14 full text ]

Prostate Cancer

"The target of arachidonic acid pathway is a new anticancer strategy for human prostate cancer." [15 ]

"Herein we provide evidence that fatty acids (FA) can trigger androgen synthesis within steroid starved prostate cancer (CaP) tumor cells..... We propose that this characterized arachidonic acid induced steroidogenesis mechanism significantly contributes to the activation of AR in CRPC progression and therefore recommend that fatty acid pathways be targeted therapeutically in progressing CaP." [16]

"The arachidonic acid pathway incorporates phospholipase, cyclooxygenase, lipoxygenase and epoxygenase enzymes. This pathway has been shown to have a major role in the development and progression of a number of cancers, including prostate cancer. We discuss the current status of research of this pathway in the area of prostate cancer, ranging from preclinical in vitro studies to human clinical trials....Evolving data suggest a significant role for some areas of the arachidonic acid pathway in prostate cancer. Inhibiting 1 or a number of these enzymes in combination may hold promise for future prostate cancer treatment." [17]

Colorectal Cancer

"Arachidonic acid metabolism through cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P-450 epoxygenase (EPOX) pathways leads to the generation of biologically active eicosanoids, including prostanoids, leukotrienes, hydroxyeicosatetraenoic acid, epoxyeicosatrienoic acid and hydroperoxyeicosatetraenoic acids. Eicosanoid expression levels vary during tumor development and progression of a range of malignancies, including colorectal cancer. The actions of these autocoids are also directly influenced by diet, as demonstrated by recent evidence for omega-3 fatty acids in colorectal cancer (CRC) prevention and/or treatment. Eicosanoids regulate CRC development and progression, while inhibition of these pathways has generally been shown to inhibit tumor growth/progression. A progressive sequence of colorectal cancer development has been identified, ranging from normal colon, to colitis, dysplasia, and carcinoma. ...Finally, novel approaches targeting these arachidonic acid-derived eicosanoids (using pharmacological or natural agents) for chemoprevention and/or treatment of colorectal cancer are outlined. "  [18]

Dietary Regulation of AA Metabolism

In the January 9, 1892 issue of Scientific American, an article stated that some members of the French  Society For The Advancement of Science believed already that "Reclus, the French Geographer, has proved that cancer is most frequent among those branches of the human race where carnivorous habits prevail."  This was before the widespread practice of raising animals on corn-based concentrated feed, suggesting that if diets rich in animal foods do increase the risk of cancer, they do so by components that occur in those foods regardless of the animal's diet, such as arachidonic acid.

More than 110 years later, scientists still find cancer risks elevated by consumption of various types of red meat [e.g. 20 full text] or poultry and eggs [e.g. 21].  Some data also suggests that fish oils may promote cancer metastases more potently than safflower oil:

"Rats were kept on either a low-fat diet or on a fish oil (omega-3 PUFAs) or safflower oil (omega-6 PUFAs) diet for 3 weeks before the administration of colon cancer cells to the portal vein, until they were sacrificed at 1 or 3 weeks after tumor transplantation. At 1 week after transplantation, the fish oil diet had induced 7-fold more metastases (in terms of number and size) than had the low-fat diet, whereas the safflower oil diet had not affected the number and total volume of metastases. At 3 weeks after tumor transplantation, the fish oil diet and the safflower oil diet had induced, respectively, 10- and 4-fold more metastases (number) and over 1000- and 500-fold more metastases (size) than were found in the livers of rats on the low-fat diet."[22 full text]

"PUFAs are incorporated into the membranes of both cancer cells and normal cells, altering their physical and functional properties (30, 39), which may interfere seriously with immunological surveillance against cancer cells. Furthermore, n-3 PUFA supplementation decreases cytokine production (40) and MHC class II expression on the cell surface of antigen-presenting macrophages (41, 42), thus interfering with the immune response (43, 44)."[22 full text]

In this study, "Fish oil and safflower oil were kept at 4°C under nitrogen to avoid autooxidation of PUFAs. Vitamin E levels in the food were kept at a minimum of 35 mg/kg of
the low-fat diet [5% (v/w) soybean oil] and at 75 mg/kg of the n-3 and n-6 PUFA diets [20% (v/w) fish oil or safflower oil. respectively] to avoid vitamin E deficiency."  Thus the ill effect of the oils in this study were not likely due to oxidation of the PUFAs.

As the amount of animal flesh, fat, and eggs in the diet increases, so does the intake of AA, which could promote AA metabolism; the more AA present in cells, the more substrate for the COX (cycloxygenase), LOX (lipoxygenase), and EPOX (expoygenase) enzymes that metabolize AA; this would result in chronic increases in PGE2 and chronic reductions in production of TNF.  As noted above [22 full text], omega-3 PUFA supplementation also interferes with immune responses involved in controlling cancer. 

This provides a couple of possible mechanisms by which a diet rich in animal flesh or eggs could support cancer development.  Briefly, chronically eating more food rich in AA would result in greater production of PGE2, which would chronically decrease production of TNF, which could reduce the control that the body has over tumor cell lines.  Eating food rich in n-3 fats (fish oils) would also depress cytokine production and MHC class II expression on the cell surface of antigen-presenting macrophages, also reducing the effectiveness of immune-system control of malignant cells.

Cancerous tumors start as single cells, and progress to detectable tumors by cell-division over the course of six to ten years.  Dr. John McDougall M.D. explains:

"The doublings remain undetectable until the cancer reaches a size of 1 mm (period-size), which now contains a million cells, after about 6 years of growth. After 10 years of growth, the tumor is 1 cm in diameter (eraser-size) and contains one billion cells. At this point in its natural history the doublings become very apparent: one billion cancer cells divide into a mass containing two billion cells, and with the next doubling there are 4 billion cancer cells inside the patient’s body. Thus, cancer is undetectable by the patient and his physician for the first two-thirds of its natural history, and this leads to confusion." [23]

Recognizing that tumors start as single malignant cells, we can appreciate how only a seemingly minor depression of immune function, e.g. a small chronic decrease in TNF production, or other alteration in the cell's environment could favor the survival of just one malignant cell, allowing it to divide to produce two, then four, then eight cells, and so on, for years, until one has a detectable tumor.


Plants provide many compounds that inhibit the COX (cycloxygenase), LOX (lipoxygenase), and EPOX (epoxygenase) enzymes that metabolize AA to PGE2 and other compounds :

"In this review, we present evidence that numerous agents identified from fruits and vegetables can interfere with several cell-signaling pathways. The agents include curcumin (turmeric), resveratrol (red grapes, peanuts and berries), genistein (soybean), diallyl sulfide (allium), S-allyl cysteine (allium), allicin (garlic), lycopene (tomato), capsaicin (red chilli), diosgenin (fenugreek), 6-gingerol (ginger), ellagic acid (pomegranate), ursolic acid (apple, pears, prunes), silymarin (milk thistle), anethol (anise, camphor, and fennel), catechins (green tea), eugenol (cloves), indole-3-carbinol (cruciferous vegetables), limonene (citrus fruits), beta carotene (carrots), and dietary fiber. For instance, the cell-signaling pathways inhibited by curcumin alone include NF-kappaB, AP-1, STAT3, Akt, Bcl-2, Bcl-X(L), caspases, PARP, IKK, EGFR, HER2, JNK, MAPK, COX2, and 5-LOX. The active principle identified in fruit and vegetables and the molecular targets modulated may be the basis for how these dietary agents not only prevent but also treat cancer and other diseases. This work reaffirms what Hippocrates said 25 centuries ago, let food be thy medicine and medicine be thy food." [24 ]

Since plants provide no AA (nor long chain omega-3 fats) but many COX2, LOX, and EPOX inhibitors, we could consider them among the "novel approaches" for preventing overproduction of the arachidonic acid-derived eicosanoids and thus "for chemoprevention and/or treatment of" cancer suggested by  [18].

We can expect that diets high in plants and low in or absent animal products would reduce the risk or even stem the growth of cancers, the latter of which has some confirmation by research I discussed here.


Other diseases linked to metabolites of AA include:

• Inflammatory bowel disease [25 full text]
• Alzheimer's disease [26]
• Ischemic heart disease [27 full text]
• Psoriasis and dermatitis [28, 29]
• Rheumatoid arthritis [e.g. 30]
• Osteoarthritis [31, 32, , 36] "Our results demonstrated that AA enhanced superoxide production in RA and OA cells..."[32]
• Migraine headaches [33]
• Dysmenorrhea (menstrual pain) and endometriosis [34]
•  Cystic disease of the breast [35]
• Osteoporosis [37]

That's just a quickly composed list.  The AA cascade drives inflammation, and chronic inflammation causes tissue damage and malfunction.

In Chinese medicine, we call inflammation pathological 'heat' (a term no less scientific than 'inflammation' which literally means 'in flames'), and land-animal meats and fats are considered common dietary promoters of conditions involving pathological heat, while many plant foods and herbs are considered 'cooling' by which we mean that they reduce or eliminate pathological heat.

Chinese physicians came to this information through logical deductions based on the yin-yang theory, combined with self-experimentation and extensive clinical experience and collaboration.  Plants have relatively yin (i.e. more water-like) characteristics like high water content, relative immobility, relative insentience, silence, low temperature, and dominance by the blue-green color spectrum, while animals generally exhibit relatively yang (i.e. more fire-like) characteristics like lower water content, mobility, greater sentience, loud sounds, inherent warmth, and dominance by the red-yellow color spectrum.

Further, the green parts of plants spend daylight hours in direct hot and drying (yang) sunlight, to which they must adapt by countermeasures that cool and moisten, so the green parts of plants must have cooling and moistening properties to survive; but animals live by burning up (oxidizing) foods, the way a fire burns up (oxidizes) fuel, so animal tissues must have fire-like oxidizing and heating properties in order to survive.

Since animals generally are more like fire (with some exceptions), and plants generally more like water, yin-yang theory predicts that many foods from animals will probably generate more heat and dryness in varying degrees (relative to plants), while many foods from plants will generally reduce heat and generate moisture.  Chinese medicine applies yin-yang theory empirically and flexibly, not dogmatically, and recognizes, for example, that some animal foods have many relatively yin characteristics (e.g. milk, mussels) while some plant foods have yang characteristics (e.g. garlic, cinnamon, chili peppers).  Thus, yin-yang theory also predicts that if a plant or animal food has atypical characteristics, like chili peppers or cinnamon bark (both red, dry, and hot), it will have corresponding effects (e.g. cinnamon will have a warming effect).  Chinese physicians tested this hypothesis with self-experimentation and then clinical application, eventually producing the current Chinese materia medica which categorizes items (mineral, vegetable, and animal) according to thermal and other effects.

The information in this article indicates that Western science supports this point of view, providing some partial biochemical explanations for the traditional Chinese medical view, i.e. arachidonic acid as a promoter of inflammation, and various anti-inflammatory plant compounds as inhibitors of inflammation.

Study Indicates Prostate Cancer Is Reversible By Diet

According to the National Cancer Institute, each year in the U.S., 240,890 men get diagnosed with prostate cancer, and 33,720 men die from it.

According to the American Cancer Society,

"About 1 man in 6 will be diagnosed with prostate cancer during his lifetime. More than 2 million men in the United States who have been diagnosed with prostate cancer at some point are still alive today.

"Prostate cancer is the second leading cause of cancer death in American men, behind only lung cancer. About 1 man in 36 will die of prostate cancer."

I have a family history of prostate cancer, so I have a personal interest in prevention and remedy for this disease of civilization.

According to some people, whole grains and legumes cause or promote the diseases of civilization, including cancer.

If this disease is caused by eating grains and legumes, then any diet based on grains and legumes should promote cancer.  If you give men living with prostate cancer a diet rich in whole grains and legumes, you should see a promotion of the cancer.

My friend, Gordon Saxe, M.P.H., Ph.D., M.D., professor of medicine at U.C.S.D.,  has actually tested this hypothesis, albeit unintentionally.

Gordon has lead pilot research in which men with diagnosed with prostate cancer were taught to eat a diet consisting of whole grains, legumes, vegetables, fruits, nuts, and seeds, while eliminating animal  products, based on evidence [discussed here] that this dietary pattern may reduce the risk or progression of prostate cancer.

If whole grains and legumes promote prostate cancer then these men should have had an accelerated progression of their cancers.  However, in the first study, over six months, this intervention produced just the opposite effect:  a 100-fold reduction in the rate of rise of their disease, as measured by the rate of change in levels of prostate-specific antigen (PSA).  As stated by Saxe et al:

"The rate of PSA increase decreased in 8 of 10 men, while 3 had a decrease in absolute PSA. Results of the signed rank test indicated a significant decrease in the rate of increase in the intervention period (p = 0.01). Estimated median doubling time increased from 6.5 months (95% confidence interval 3.7 to 10.1) before to 17.7 months (95% confidence interval 7.8 to infinity) after the intervention. Nine of 10 participants in the study had reduction in the rate of rise of their PSA, a marker for progression of disease."

When 9 of 10 people respond in the very same way to an intervention, in this case with a reduction in rate of rise of PSA, this tends to suggest that the effect is no accident and most likely indicates a definite therapeutic effect of the intervention.

In the second study, involving 14 men, Saxe et al produced a similar result.  In this second study they explored the biological mechanisms involved:

"During the first 3 months of the intervention, as both median WHR and body weight declined significantly, the median rate of PSA rise not only declined but became negative, reflecting a slight reduction in absolute PSA and possibly disease regression in patients with absolute reductions. Conversely, during the second 3 months of the intervention, when median body weight increased (though not significantly), median PSA began to rise again, albeit more slowly than during the period prior to Baseline."

This second study suggested that weight-related metabolic changes may have mediated the reduction in rate of PSA increase.  In other words, the intervention resulted in a loss of body fat and concommitant metabolic changes related to reduction of body fatness, including an increase in sex hormone binding globulin, that influence prostate cancer.

"Assuming that the attenuation of PC progression was mediated by weight-related metabolic changes, a question arises as to what aspect of intervention brought about the observed reduction in adiposity. Earlier ⁵³, we described large increases during months 0–3 in intake of whole grains and vegetables, food groups which are fiber and water-rich, very low in fat, and therefore of low energy density. However, intake of these foods declined slightly during months 3–6. Weight loss during the first three months may possibly have resulted from replacing energy-rich foods with energy-poor foods, and the slight increase in body weight during the second three months may have resulted from a small degree of dietary recidivism." 

So this intervention, based on increasing intake of whole grains, legumes, etc., resulted in body fat reduction during the period when the subjects ate the most of these foods, and body weight increased during the period when these subjects ate less of these foods.  This clearly undermines the idea that diets rich in grains and legumes cause two of the major diseases of civilization, i.e. obesity and cancer.

Saxe et al consider the possibility that any diet that induces weight loss may reduce cancer progression.

"A second question that naturally arises regarding the reduction in adiposity is whether it matters, in terms of effects on prostate cancer progression, how it is achieved. One aspect of this question has to do with the preferred dietary strategy for reducing energy intake. Another facet regards whether it is more desirable to increase energy expenditure or decrease intake to achieve this end. Although our study and its findings did not address these issues, they remain important ones that warrant consideration in the planning and design of future behavioral approaches to the management of progressive PC. What can be said is that while both a plant-based diet and a high-protein, low-carbohydrate diet high in foods of animal origin (such as the popular Atkins diet) may both result in weight loss, the former is far more consistent with the dietary cancer prevention guidelines of various agencies (69).⁵⁴ "

Some people reject those cancer prevention guidelines of various agencies, which emphasize increased consumption of whole plant foods and decreased consumption of animal products, claiming that whole grains and legumes are the true causes of diseases of civilization.   These two studies, among others, weaken that claim. 

So far, the only studies I can find testing the effect of a low-carbohydrate diet on prostate cancer were done with mice, not men.  In this one, researchers from Duke Prostate Center fed mice with prostate cancer either a "Western" diet,  "low-fat high-carbohydrate" diet, or a zero-carbohydrate diet.  The results:

"Fifty-one days after injection [with xenograft tumors], NCKD mice tumor volumes were 33% smaller than Western mice (rank-sum, P = 0.009). There were no differences in tumor volume between low-fat and NCKD mice. Dietary treatment was significantly associated with survival (log-rank, P = 0.006), with the longest survival among the NCKD mice, followed by the low-fat mice."

I don't have access to the full text, but if done in a typical fashion, all diets would have been pellets made from isolated nutrients (e.g. casein, starch, sugar, etc.) so this can't tell us much about what would happen in humans if we compared a whole foods vegan diet (whole grains, legumes, vegetables, fruits, nuts, seeds) to a zero-carbohydrate diet (meat and fat only).  The effects of a casein-based zero-carbohydrate diet on mice might be very different from the effects of a meat-based zero-carbohydrate diet on humans.

In a second study, Masko et al fed mice diets containing 0, 10, or 20 percent carbohydrate and again injected them with prostate cancer cells.  As a 'control' they fed a group of mice a 12% fat diet, but they did not inject cancer cells into these mice--which to me means they weren't much of a control group, because they differed from the others not only in dietary composition but also in absence of tumor injection.

The full text of this study tells us the components of all diets:  corn oil, lard, milk fat, casein, dl-methionine, dextrine, maltodextrine, corn starch, sucrose, and isolated vitamins and minerals. 

In the low-fat arm, 72% of calories came from carbohydrate, and 50% of total calories came from sucrose, which means that about 25% of total calories came from refined fructose.  Meanwhile, in the 10% and 20% carbohydrate arms, all of the carbohydrate was provided in the form of corn starch. 

This makes me wonder again about diet composition in the other Duke University study cited above.  Were those mice on the low fat diet also eating a 50% sucrose/25% fructose diet?  If so, did this rig the study, intentionally or not, so that the low fat group would have more body fat and shorter lifespan than the zero-carbohydrate group? 

Moving on, all the mice got all of their protein from casein-plus-methionine, none ate any meat.  Most people eating low carbohydrate diets eat cooked meats, not isolated casein, as their main protein source.  Meat is nutritionally complex, and affected by cooking process, in ways that may result in it having a different effect on prostate cancer than casein-plus-methionine.  For example, unlike the casein-methionine mix fed to these mice, meat contains heme iron and if cooked at high heat, heterocyclic amines, all of which have been linked to prostate cancer causation or promotion [e.g. Sinha et al full text].  So it is not clear how a study of mice eating a low carbohydrate diet wherein casein is the main protein will apply to people eating low carbohydrate diets wherein cooked meat, poultry, and fish are the main protein sources.

Masko et al found that the survival rates of the mice in the 0, 10, and 20 percent carbohydrate groups were similar.  They liked this finding because, as they say, people find it extremely difficult to follow zero-carbohdyrate diets, so now they are ready to test the 20 percent carbohydrate diet on human prostate cancer patients. 

Masko et al also found that the mice in the 20% carbohydrate group had the lowest insulin level, about which they comment:

"It was unexpected that the lowest levels of insulin were observed in mice fed with 20% carbohydrate, but there are possible explanations for this phenomenon. First, there is always the possibility for a type I error in the analysis. Second, it is known that low-carbohydrate diets promote insulin sensitivity in animals (38) and humans (39, 40). Thus, it is possible that a diet containing a small amount of carbohydrates may actually improve insulin sensitivity compared with a diet completely lacking of carbohydrates."

Perhaps unknown to Masko et al, it is also 'possible' that a diet containing an even large amount of carbohydrate may actually improve insulin sensitivity compared to a diet with only 20% carbohydrate. In 1971, Brunzell et al [abstract only] evaluated the effect of increased dietary carbohydrate at the expense of fat in humans, both non-diabetic and mildly diabetic.  In the New England Journal of Medicine they reported that after feeding these subjects a diet providing 85 percent of energy as carbohydrate for 10 days,

"Fasting plasma glucose levels fell in all subjects and oral glucose tolerance (0 to 120-minute area) significantly improved ..... Fasting insulin levels also were lower on the high carbohydrate diet; however, insulin responses to oral glucose did not significantly change. These data suggest that the high carbohydrate diet increased the sensitivity of peripheral tissues to insulin."

 An diet supplying 85 percent of energy as carbohydrate is by necessity very low in fat, so perhaps Brunzell et al could have emphasized that this very low fat diet increased insulin sensitivity.  The mice of Masko et al that got the 20 percent carbohydrate diet had a lower fat intake than the mice on the zero-carbohydrate diet; rather than increasing carbohydrate being responsible for promoting insulin sensitivity, perhaps it is reducing fat (replacing it with starch) that does the trick. 

Anyway, the Masko et al study has a few features that make me skeptical that they will have similar results in humans.  I feel curious to see if their approach will have results as good as those found by Saxe et al.