I began writing this yesterday after seeing the Daily Mail headline:
- "Fatty Western diets make prostate cancer more aggressive"
This from a newspaper that advised men to drink flaxseed oil to avoid PCa. Ugh!
After a while, I became weary of the subject & the stupidity of the media, so listened to some music instead.
Anyway, Kuanyin's post:
- "It's The Fat, Stupid!"
has drawn me back in. Rather than replying to him with a post that would not be read by those who have already read his post & moved on, this is a separate thread.
...
In the Pandolfi-Chen study [1], we discover something interesting about metastatic PCa.
It is common knowledge that PTEN is often inactivated in PCa.
Note: PTEN (phosphatase and tensin homolog) is a tumor suppressor gene. [2]
There are over 1,300 PubMed hits for <prostate PTEN>. We know a lot about PTEN.
[3] (1997) - Johns Hopkins - "Frequent inactivation of PTEN/MMAC1 in primary prostate cancer."
[4] (2017) - Netherlands/USA - "PTEN loss is associated with prostate cancer recurrence and alterations in tumor DNA methylation profiles."
& so on.
We know far less about PML (promyelocytic leukaemia), which is also a tumor suppressor gene.
From what I read in the study abstract [1], it is possible to have PTEN-null indolent PCa, but if PML is silenced too, the cancer becomes aggressive. AND, this involves the cancer cells manufacturing lipids. At least in the mouse model.
Note: Yes, PCa is able to make fats. To do this, it needs enzymes from the fatty acid synthase [FAS] complex. Back in 1995, Partin at Johns Hopkins reported [5] that FAS "predicted pathologic stage well when analyzing primary prostate cancer in radical prostatectomy specimens" & "is one of the few markers that provides additional predictive information beyond that of the Gleason score".
[6] (2017 - Russia) - "the high frequency of FASN expression in hPIN and cancer and no expression in most structures of benign hyperplasia make it possible to use this protein as an additional marker in the differential diagnosis of prostatic neoplasms."
So we can infer that prostate cells normally do not make fatty acids, & that the extent of FAS expression is indicative of how aggressive the cancer is.
[7] (2017) - U.S. - "Increased de novo synthesis of fatty acids is a distinctive feature of prostate cancer ... Therefore, inhibition of de novo fatty acid synthesis represents an attractive strategy for chemoprevention of prostate cancer. We have shown previously that dietary feeding of phenethyl isothiocyanate (PEITC), a phytochemical derived from edible cruciferous vegetables such as watercress, inhibits incidence and burden of poorly differentiated prostate cancer in transgenic adenocarcinoma of mouse prostate (TRAMP) model."
"The current study is the first to implicate inhibition of fatty acid synthesis in prostate cancer chemoprevention by PEITC."
So far, we have seen that the fat problem is a PCa cellular issue, & that the solution perhaps involves inhibition of FAS, & that we might be able to do that by consuming watercress.
Note: When cruciferous vegetables are cooked, the enzyme that liberates the active chemical is destroyed. Fortunately, watercress is usually eaten raw. The best way to liberate the maximum amount of PEITC is via a blender. Chewing is hit or miss, especially with my teeth. One approach I have used is to fill an ice cube tray with puree. Allow a cube to thaw each day before a fatty meal & swallow the stuff with the meal. The fat in the meal is essential for uptake.
...
How did a study about PTEN & PML suddenly segue to a "Western HFD" (high fat diet)?
The research team seems to have had a Eureka moment when they discovered the importance of PCa-manufactured fatty acids. "What if fat is the problem?" So they fed the mice a high fat diet, which made the cancer more aggressive.
The thinking, methods & language of these guys is so sloppy, that I am tempted to go back to my music in disgust.
What is a "Western HFD"? It is well known (& oft repeated) that Asians rarely get PCa until they move to America & adopt a Western diet. My experience of immigrants in the U.S., such as it is, is that we do not stray that far from our native diets. What changes with migration is affluence - we eat a little more of something & a little less of something else. One need only look at the increasing rate of PCa in the expanding middle classes in certain parts of the world. A frugal peasant diet is PCa-protective, it seems.
What is meant by a "Western HFD", as opposed to an Inuit HFD, say, which happens to be protective? The common definition is that it includes high-fat dairy.
In 2016, when my wife was seriously ill, I became well-acquainted with local supermarkets. The dairy aisles had an amazing selection of plain yogurt (one of the few things that my wife could then tolerate). Every brand had a 2% & zero fat version, but only one also had a product that was not fat-reduced. One supermarket did not have any full-fat yogurt at all.
& the aisles were full of NO-Fat & LO-Fat products. Raw meats were trimmed of almost all fat. & so on.
It's the logical conclusion of the Ancel Keys campaign against saturated animal fat - the vilification of fat itself. The U.S. food pyramid has fat at its apex & grains at the base. The fatter the population becomes, the more people turn to the pyramid, & fat-free products. What exactly is an American "Western" diet at this point?
Anyway, the study authors seem to buy into "the notion that a Western HFD can promote metastasis." So they fed the mice a HFD. What does HFD mean, in a murine context?
We have a number of old mice studies that showed that you could always improve survival by reducing the fat content of the diet.
Steve Freedland, who has been involved in some important studies, asked a simple question - does the type of fat matter? He discovered that the fat in commercial chows used by labs was corn oil. Does anyone here use corn oil anymore? It is high in linoleic acid [LA] a pro-inflammatory omega-6 fatty acid, precursor of the deadly arachidonic acid [AA] that is freely taken up by PCa cells when there is little or no omega-3 EPA-DHA.
[8] "Epidemiologic studies suggest that increased dietary fat consumption has a negative effect on PCa outcomes; however, it is unclear to what extent the type of dietary fat consumed influences disease initiation and progression. Indeed, both population-based and xenograft studies have suggested that fish oil consumption decreases PCa risk. Other studies have shown that, when using a corn oil-based diet, decreasing total dietary fat increases survival in a xenograft model. In contrast, another study demonstrated no improvement in PCa outcome when the amount of dietary fat was decreased using a saturated fat-based diet. This raised the hypothesis that, in addition to the amount of dietary fat being important, the type of fat mattered too. Thus, we sought to systematically examine the effects of various types of fat on PCa progression. We found that male mice xenografted with LAPC-4 tumors fed a diet in which the dietary fat source was fish oil outlived mice fed diets composed of corn oil, olive oil, or animal fat; survival was similar across the non-fish oil groups."
In the new study, it is meaningless to speak of a high fat diet without specifying the fatty acid components.
...
For those who are taken in by the headlines resulting from the new study, a 10% fat Dean Ornish vegan diet is the obvious next step.
Cows are vegan. Grass-fed cows don't build a lot of fat, but the fat is not from the diet. Most beef cattle in the U.S. go to feed lots before slaughter. They are typically fed corn &/or soy to fatten them up. The idea of a high carbohydrate diet causing fat accumulation shouldn't seem that odd.
What happens when we eat a carbohydrate meal? Digestible carb turns to glucose. It can happen fast or it can happen slow, but there will be a glucose spike in the blood. The body acts quickly to get rid of the spike. The response includes an insulin spike to get glucose to cells that can use it. The kidneys will try to get rid of some of it. But, alas, the basic strategy is to get the glucose stored as fast as possible & out of the blood. The glucose is first converted to triglycerides & preferentially stored as visceral fat.
[9] "Excess carbohydrates in the body are converted to palmitic acid. Palmitic acid is the first fatty acid produced during fatty acid synthesis and is the precursor to longer fatty acids. As a consequence, palmitic acid is a major body component of animals. In humans, one analysis found it to make up 21–30% (molar) of human depot fat"
It is ironic, that the more people stricly follow the food pyramid, the more fat the body creates. When there is a significant amount of fat in a meal, glucose enters the blood slower, over a longer period, & without the spike.
Conversely, the body does not respond with urgency when a high fat meal is eaten. There is no rush to store circulating fatty acids, & they are largely used directly for energy.
...
When Dr. Myers first began treating PCa, he favored a low-fat diet. He quickly switched to a Mediterranean diet, which is 40% fat. In a vlog post he said that his patients who remained on a low-fat diet did not do well.
There is a study in an older post where PCa benefit was shown in a Mediterranean diet with nuts. Nuts are high in fat, so I guess that Dean Ornish doesn't include many in his 10% fat meals. Nuts contain varying amounts of fat & have distinct fatty acid profiles. One needs to be aware of how profound fatty acid differences can be.
If Ancel Keys could have pointed to the most dangerous saturated animal fatty acid, he might have fingered stearic acid. It has a backbone of 18 carbons, each of which is fully hydrogenated. They make candles out of the stuff.
But let's make the smallest of modifications - dehydrogenate at the halfway point. That turns it into an omega-9 monounsaturated fatty acid. Instead of being rigid, it bends in the middle. The result is oleic acid, the major fat in olive oil. The supremely healthy fat, according to some.
In recent years, stearic acid has been found to be neutral in turns of cardiovascular health. The body can convert stearic acid to oleic acid (& vice versa). In many cancers, though, including PCa, the oleic:stearic ratio directly correlates with a poorer prognosis. Cancer seems to like oleic acid but not stearic acid, & I doubt that diet affects that.
It's a complicated subject because the body has its own ideas about the fatty acids it needs, & it can create most of them. The exceptions are the omega-6 & omega-3 fatty acids. That is one area where we have control.
-Patrick
[1] nature.com/articles/s41588-...
[2] en.wikipedia.org/wiki/PTEN_...
[3] ncbi.nlm.nih.gov/pubmed/937...
[4] ncbi.nlm.nih.gov/pubmed/291...
[5] ncbi.nlm.nih.gov/pubmed/781...
[6] ncbi.nlm.nih.gov/pubmed/284...
