Tuesday, January 29, 2008

Colorectal cancer and cholesterol

Because I'm quite interested in colorectal cancer I've had this abstract lying around on my desktop for some time, awaiting full reading before "drag and drop" in to that enormous and chaotic folder labeled "Diet stuff".

OK, the usual caveats apply; it's observational and it's a bit of a data trawl from the Cardiovascular Health Study. Hmmm, this means that cardiologists are involved in the data acquisition. Bad.

On the plus side it's prospective and no drug company is involved. US government funded. It's also available in full text, which is nice because it means I can work through their results and see if their conclusions are derived from their findings.

You know how it is, you browse down these tables slotting yourself in to the various groups and... Ooooh, they measured cholesterol levels! Now there's a surprise. Did you notice any mention of cholesterol levels in the abstract? Particularly that killer LDL cholesterol?

No, neither did I.

LDL-C got its little section as the penultimate parameter in table 2. Let's read the table, the bit we want is down at the bottom. And the risk of colorectal cancer is:

LDL-C quartile and risk of colorectal cancer:

Lowest.......1.0 (reference value)

The absolute numbers were, from lowest to highest, 35/1447, 26/1416, 23/1467 and 16/1386 incident cancers.

The relationship is remarkably linear, p = 0.01

None of the other parameters (fasting glucose or glucose 2h post OGTT) did any better than p = 0.02. But they got in to the abstract. And in to the title too!

The LDL-C association did get a brief mention in the discussion:

"Surprisingly, a strong association between increased LDL levels and decreased risk of colorectal cancer was identified. The explanation for this finding is unclear."

That's it.

That's the total discussion of their most statistically significant finding. Possibly their most biologically significant finding.

The lowest quartile for men had LDL-C below 100mg/dl, women below 110mg/dl. Those were the ones most likely to get bowel cancer. I think it's worth pointing out that the average cardiologist would consider an LDL-C of 100mg/dl or above as a peracute statin deficiency. That lowest quartile is where your cardiologist wants you to be.

BTW I'm in the highest LDL-C group. Just as well, with my family history.

Just assuming, for a split second, that there is causality between low LDL-C and colorectal cancer, would you expect statins to trade heart attacks for cancer? Pravastatin perhaps? I posted the body counts here.

Anyone chosen between heart attack and bowel cancer yet?

The last author on this paper is Savage. He's surprised at the association. Why should he be? He helped write the guide to treating metabolic syndrome for the US government. He would be expected to have read the literature. Maybe.

Obviously he wouldn't read an Irish paper:

"A group of 114 Irish patients with primary adenocarcinoma of the large bowel had significantly lower serum cholesterol concentrations than an age and sex matched group drawn from the general population"

or a Brazilian paper:

"Our study suggests an association between low blood cholesterol and colorectal cancer"

or an Austrian paper:

"low cholesterol was significantly associated with all-cause mortality, showing significant associations with death through cancer, liver diseases, and mental diseases"

or a Japanese paper:

"The J-curve association was observed between average TC or LDL-C concentrations and total mortality. Malignancy was the most prevalent cause of death. The health of patients should be monitored closely when there is a remarkable decrease in TC and LDL-C concentrations with low-dose statin"

or even stuff from Honalulu:

"Only the group with low cholesterol concentration at both examinations had a significant association with mortality (risk ratio 1.64, 95% CI 1.13-2.36). INTERPRETATION: We have been unable to explain our results. These data cast doubt on the scientific justification for lowering cholesterol to very low concentrations (<4.65 mmol/L, 181mg/dl) in elderly people"

But, for crying out loud, you would have thought he would have memorised chunks of Keys as part of his cardiology training!


"Among 477 cancer deaths five years after cholesterol measurement, there was a significant excess of lung cancer deaths in the bottom 20% of the cholesterol distributions in the populations"

How about NHANES1:

"The inverse cholesterol-cancer relation in men was present for cholesterol determinations made 6 or more years before diagnosis of cancer"

or even Framingham:

"Although the Framingham data are not conclusive, they do suggest that in some cancer cases where the serum cholesterol level was lower than that expected at as much as 16--18 years before cancer diagnosis, the depressed level was likely to be a precursor to the tumor growth"

Surprised is he?

That's enough. I was looking for information about glucose and cancer and yet again ended up grinding my teeth on the stupid cholesterol hypothesis and its followers.

I'll calm down now.



Stephan Guyenet said...

Nice compilation of data! The thorn in the side of the low-cholesterol mafia is that lowering total cholesterol doesn't improve all-cause mortality risk. Replacing saturated fats with polyunsaturates either has no effect on overall mortality or increases it (based on my reading), despite lowering total cholesterol.

However, it seems to reduce heart disease risk a bit, which they have decided is the only outcome that matters. The problem is it also seems to increase the risk of cancer and violent death.

It makes no sense to me that we would be healthier eating a type of food that isn't natural to our species, than eating a type that is. I will always be very skeptical of any claim that a modern, processed food or unnatural macronutrient balance is healthy. I think a lot of people have egg on their faces for ignoring our evolutionary context. Trans fat margarine comes to mind.

John Speno said...

Hi Peter,

I just started reading Hyperlipid recently and I wanted to say thank you for writing it. It's brilliant!

Anonymous said...

Peter, I'm wondering why you have a high cholesterol level. Kwasniewski says that everybody eating his diet has low cholesterol after they have adapted to it. Hunter-gatherers all have low cholesterol too as Cordain often notes. So, it seems that this alleged "risk" from low cholesterol level is an artifact of the typical modern processed food diet. And the "protection" of high cholesterol is only in the same dietary context as well. Once you step outside of that paradigm, all bets are off, I would say. Low cholesterol can be healthy if you are eating high animal fats, low PUFAs, low carbs, etc.

Peter said...

Hi Bruce,

Yes, it's open to speculation as no one has looked at high/low cholesterol outside the current dietary experiment we're living through. I'm dubious that my own cholesterol level is primarily diet related. My wife, who is just over half my age, has a TC in hunter gatherer ranges which would make Cordain happy (can't remember the number, we just once ran it through the in-house analyser). We eat the same food. I really don't believe low TC is bad under these circumstances.

Heterozygous FH certainly confers survival advantages on a sepsis basis. So IF (big if) the main problem with FH is that it means you cannot deliver LDL-C to the endothelial cells which need it for damage repair, then FH becomes a genetic trait which is a liability under a sugar/PUFA based (vascular damaging) diet environment.

There are so many FH variants that testing is not an option. My best option seems to be to check on vascular health and my current thinking is that EBCT might be the best way to look at the end result of living with it. Got to sell my motorbike first.


Anonymous said...

Don't get me wrong. I'm not arguing that high cholesterol is dangerous. I'm just pointing out that the idea low cholesterol is harmful has some flaws when taken outside the modern dietary context. Some people - like Colpo and Ravnskov - try to have it both ways. They point out that some groups had low cholesterol, despite eating lots of saturated fats. Then they turn around and say that "high cholesterol is protective." They're committing the same fallacy they're accusing the other side of.

Depending on the individual, having high or low cholesterol may be good or bad or neutral. If you're eaitng the Prudent Diet, low cholesterol's probably bad. If you're eating fast food and junk food, low cholesterol might also be bad. Outside of that, there are many confounders.

Peter said...

The other source of information is Lutz, He suggests that people over 40 do not have a drop in TC with his level of carb restriction (70g/d), where as people under 40 do. Probably under 30 years of age they drop even more. The question then is what will TC do in a young LC eater who is weight stable at preferred BMI as the years progress. And does it matter provided glucose and insulin are under control anyway? I don't see this being studied anywhere at the moment! Or in the near future.


Dr. Curmudgeon Gee said...

this issue is very personal to me.

next time i'll have Lord Hubby bring these references to his (well meaning) doc for his "statin deficiency" XD


Stonetica said...

High HDL. I know this is an old string, but am just hoping you can offer an opinion without your having to do more research. I have always had very high HDL. My last numbers were TC 242, HDL 128, and LDL 106. I don't believe it has anything to do with my diet as that has swung between high sugar/grains, to low carb. My dad died with colorectal cancer.

Stonetica said...

High HDL. I know this is an old string, but am just hoping you can offer an opinion without your having to do more research. I have always had very high HDL. My last numbers were TC 242, HDL 128, and LDL 106. I don't believe it has anything to do with my diet as that has swung between high sugar/grains, to low carb. My dad died with colorectal cancer. I'm not asking why my numbers are as they are, but for an opinion on how my high TC and lowish LDL fit into the cancer picture.

Peter said...

Hi Stonetica,

Sorry to be so long, been doing non blog things.

The main problem I would think about with your lipids is that there is clearly something amiss with a cholesterol transfer protein, your lipids look like those of a person on Torcetrapib:


The only tool I can think of to deal with this would be damage limitation (never become hyperglycaemic) and limit stimulation of the growth of cancers (don't drop insulin on to cancer cell ILGF-1 receptors). I guess limiting polyunsaturated fats would help too as these have core metabolic effects which block the ability of a given cell to avoid overproducing energy currency (such as NADH) which appear to set the stage for cancer growth.

But these are my generic approaches to health anyway...


BTW I also wonder if you have very low levels of Lp(a). This mops up oxidised cholesterol derivatives, carefully hoards them, then throws them at cancer cells. But again, if you lack this tool, prevention becomes key.