Someone asked for a post on sugar. If it doesn't cover what you had in mind, let me know. -Patrick
Sugar & Cancer.
A. Overview.
A1.The Sugar Myth.
One of the enduring myths about cancer, is that sugar causes and/or feeds cancer. Countless internet sites advise the unwary to give up sugar. Going easy on sugar is an excellent idea, but abstainers may have the misguided impression that they are preventing or starving cancer.
The body tightly regulates the level of glucose in the blood. If we could bring glucose down below the normal range, we would be inducing hypoglycemia, which is no fun at all. And we would be starving the brain – a big & the most important user of glucose.
It is true that cancer cells generally have an increased appetite for glucose, but availability does not drive usage. The cancer cells take what they want, just like other cells.
The preferred fuels used by normal prostate cells are fatty acids – not glucose. With other cancers a PET scan with radio-labeled glucose can be used. This is not effective for prostate cancer, which continues to favor fatty acids.
A2.Sugar & Insulin Resistance.
The reason for being wary of sugar is that glucose spikes can lead to insulin resistance, & may lead to diabetes. Insulin resistance is one of the markers of the Metabolic Syndrome. [MetS]. MetS is associated with many chronic diseases – particularly cardiovascular.
Surprisingly, while diabetics get more cancer of every other type, they get less prostate cancer.
In the pre-diabetic state, the body produces more insulin to try to overcome the loss of insulin sensitivity. In the diabetic state, insulin-producing cells have burned out & the body can no longer meet the demand.
This suggests that insulin may be an important driver of prostate cancer. It is therefore prudent for men to rein-in insulin production.
Here is a simple guide for insulin sensitivity status:
-If Triglycerides are close to the HDL-cholesterol number … Excellent.
-If Triglycerides are getting close to twice the HDL-cholesterol number … Not ideal.
-If Triglycerides are more than double the HDL-cholesterol number … Make changes to the diet.
Why triglycerides? The body gets rid of excess glucose be converting it to triglycerides & storing it in fat cells.
A3.Why the emphasis on sugar?
Table sugar consists of units of glucose joined with units of fructose. When broken apart, the glucose is readily taken up into the blood. But the biological fate of all carbohydrate is glucose. With simple carbs, glucose appears in the blood faster. The conventional advice is to eat complex carbs, but they end up as glucose too, & can elevate glucose levels.
Fat slows down the digestion of carbs. Supermarkets are full of NO-FAT & LO-FAT products, but people still have problems controlling their weight. The problem is a food pyramid that places carbs at the very bottom & fat at the very top.
The 10% fat, high-carb diet promoted by Dean Ornish actually increases triglycerides. One can lose weight on his diet, since he recommends carbs that have a lot of fiber. This is really a way of reducing calories by adding bulk to meals. But triglycerides due to glucose spikes are preferentially stored as dangerous visceral fat. The Ornish-type diet can lead to the LOFI phenomenon – Lean Outside, Fat Inside.
Fat around the prostate is associated with more aggressive cancer.
B.Sugar – More Detail.
B1.Otto Warburg.
Nobelist Otto Warburg is usually cited by those warning about sugar’s role in cancer. He is often misunderstood or misrepresented, but he did persist in a view of cancer that is not held today:
“Cancer, above all other diseases, has countless secondary causes. But, even for cancer, there is only one prime cause. Summarized in a few words, the prime cause of cancer is the replacement of the respiration of oxygen in normal body cells by a fermentation of sugar.” [B1]
It is true that cancer often switches to anaerobic respiration, but Warburg put the cart before the horse.
The fact that cancer switches to an inefficient process that necessitates a higher uptake of glucose (the Warburg Effect), has led people to suppose that dietary sugar directly drives cancer growth. Not so.
B2.What does the medical profession say?
Memorial Sloan Kettering [B2a]:
“There’s a lot of confusing and misleading information on the Internet about the relationship between sugar and cancer. The notion that refined sugar causes cancer or that cutting sugar from the diet is a good way to treat cancer are two common — and incorrect — claims that turn up in a Google search.”
Mayo Clinic [B2b]:
“Fact: Sugar doesn't make cancer grow faster. All cells, including cancer cells, depend on blood sugar (glucose) for energy. But giving more sugar to cancer cells doesn't speed their growth. Likewise, depriving cancer cells of sugar doesn't slow their growth.”
B3.Aerobic & Anaerobic respiration.
Aerobic: Glucose + Oxygen = Carbon Dioxide + water + maximal Energy
Anaerobic: Glucose = Lactic Acid + minimal Energy
Cells switch from Aerobic to Anaerobic when oxygen is low. This can happen during excessive exercise. And one expects it to happen when tumors outgrow their blood supply & become hypoxic. But cancer cells often switch to anaerobic respiration even before oxygen becomes scarce.
The crazy thing about that is the degree of inefficiency. “Aerobic metabolism is up to 15 times more efficient than anaerobic metabolism” [B3a]. Fast dividing cancer cells need more energy than normal cells, so it’s easy to see why radio-labeled glucose (FDG: Fludeoxyglucose) would give a clear image on a PET scan when anaerobic respiration is being used. They are sucking up a lot of glucose.
FDG PET is not used for PCa. From a 2001 study [B3b]:
“FDG PET studies were negative in 23 of the 24 organ-confined prostate cancers and the study was only faintly positive in 1 tumor (4.0% sensitivity).”
“FDG PET is not a useful test in the evaluation of clinically organ-confined prostate cancer.”
PCa cells prefer fatty acids [B3c] [B3d]:
“Uptake of palmitate in all 3 prostate cell lines was significantly higher than that of glucose at all incubation times”. “Prostate cells are characterized by a dominant uptake of fatty acid over glucose”
“Most malignancies have increased glycolysis for energy requirement of rapid cell proliferation, which is the basis for tumor imaging through glucose analog FDG (2-deoxy-2-fluoro-D-glucose) with positron emission tomography. One of significant characteristics of prostate cancer is slow glycolysis and low FDG avidity.”
“Several enzymes involved in the metabolism of fatty acids have been determined to be altered in prostate cancer relative to normal prostate, which is indicative of an enhanced beta-oxidation pathway in prostate cancer. Increased fatty acid utilization in prostate cancer provides both ATP and acetyl-coenzyme A (CoA); subsequently, increased availability of acetyl-CoA makes acceleration of citrate oxidation possible, which is an important energy source as well. Dominant fatty acid metabolism rather than glycolysis has the potential to be the basis for imaging diagnosis and targeted treatment of prostate cancer.”
B4. Carbohydrates, Insulin & Triglycerides.
Although sugar neither causes cancer nor feeds it, there is a plausible link between glucose & prostate cancer. Chronic glucose spikes can lead to insulin resistance, which, in the pre-diabetic, means elevated levels. Insulin is a PCa growth factor.
The body does not like blood glucose to be elevated. Insulin is supposed to facilitate the removal of circulating glucose into tissue. When insulin is chronically elevated, tissues become resistant. One way around this is the conversion of glucose to triglycerides, which are then stored in fat cells.
The American Heart Association [AHA] [B4a]:
“A high triglyceride level combined with low HDL cholesterol … is associated with atherosclerosis, the buildup of fatty deposits in artery walls that increases the risk for heart attack and stroke”
The triglycerides:HDL cholesterol ratio is actually a measure of insulin resistance [B4bi] [B4bii]:
“TG/HDL-chol ratio, a surrogate marker of insulin resistance”
“In apparently healthy subjects, elevated TGL/HDL ratio was significantly associated with the presence of IR.”
Wikipedia [B4c]:
“Diets high in refined carbohydrates, with carbohydrates accounting for more than 60% of the total energy intake, can increase triglyceride levels.”
In a low-fat setting, carbohydrates are converted to glucose too quickly. Carbs can quickly end up as stored fat (triglycerides) when there is insulin resistance.
Doctors look at fasting triglycerides of up to 150 mg/dL as being normal, whereas the AHA prefers the cap to be 100 mg/dL. I think that is more prudent. With an HDL-cholesterol of 50, say, & using the quick guide above, triglycerides in the 50-100 range would be OK, although close to 50 would be best.
In a 1992 dietary intervention study comparing high & low carb diets [B4d]:
“Compared with the low-carbohydrate diet, the high-carbohydrate diet caused a 27.5% increase in plasma triglycerides and a similar increase in VLDL-cholesterol levels; it also reduced levels of HDL cholesterol by 11%.”
So, with the high-carb diet, triglycerides & HDL-cholesterol go in the wrong direction, with the insulin resistance ratio increasing by 43% in this study.
On top of that, there is a big jump in the VLDL- cholesterol level. We would be less concerned about LDL-cholesterol if it were all carried by the larger particles, but the small VLDL fraction of LDL allows the cholesterol to be carried to places where you don’t want it to go, such as into arterial walls.
VLDL-cholesterol is an issue in PCa, where it can readily pass into cells. Cancer cells like to accumulate cholesterol. This has an added significance in PCa, where cholesterol can be used directly to manufacture androgens.
B5.PCa & Insulin Levels / Insulin Resistance.
In a Finnish study [B5a]:
“Among subjects in the second through fourth insulin quartiles, compared with those in the first quartile, increased insulin levels were associated with statistically significantly increased risks of prostate cancer {risk factor = 1.50, 1.75, & 2.55} for the second through fourth insulin quartiles, respectively”,
“Elevated fasting levels of serum insulin (but not glucose) within the normal range appear to be associated with a higher risk of prostate cancer.”
In a Chinese study [B5b]:
“… men in the highest tertile of insulin resistance had an increased risk of prostate cancer {risk factor = 2.78}. ”
In a U.S. study [5Bc]:
“Increased serum insulin associated with increased risk of prostate cancer recurrence.”
“the insulin levels of high risk patients were significantly higher than the insulin levels of medium and low risk patients”.
In a Swedish study [B5d]:
“In conclusion, hyperinsulinaemia and five other previously established components of metabolic syndrome are shown to be prospective risk factors for deaths that can be ascribed to prostate cancer. These findings confirm previous study, which indicate that prostate cancer is a component of metabolic syndrome. Moreover, these data indicate that hyperinsulinaemia and other metabolic disorders precede deaths caused by prostate cancer. Thus, our data support the hypothesis that hyperinsulinaemia is a promoter of clinical prostate cancer. Furthermore, our data suggest that the insulin level could be used as a marker of prostate cancer prognosis and tumour aggressiveness, regardless of the patient's prostate cancer stage, cancer grade and PSA level.”
B6.PCa & Triglycerides.
In a Swedish study [B6a]:
“… we found a positive association between triglycerides ≥2.25 mmol/L and PSA levels >20 μg/L {risk factor = 1.17}, as compared to PSA levels of 4.0–9.9 μg/L.”
Note: 2.25 mmol/L = 200 mg/dL.
In an Argentine study [B6b]:
“Patients with PCa showed higher TG/HDL-chol and diminished HDL-chol than Controls and BPH. PSA correlated inversely with HDL-chol and directly with TG/HDL-chol.”
Note: TG = Triglycerides; HDL-chol = HDL-cholesterol.
In a U.S. study [B6c]:
“Elevated serum triglycerides were associated with increased risk of prostate cancer recurrence {risk factor per 10 mg/dl = 1.03}”
B7.Periprostatic Fat (fat around the prostate)
There are many studies, but they say the same thing. Here’s the latest [B7a]:
“A higher periprostatic fat ratio is significantly associated with a higher Gleason score. Periprostatic fat ratio is a better predictor of higher Gleason score compared with periprostatic fat volume and may be an important risk factor in diagnosing patients with higher grade prostate cancer.”
The problem with visceral fat is that it is hormonally active. Fat isn’t just a store, it can interfere with internal organs in a paracrine fashion. Fat secretes a number of hormones, but estradiol might be particularly important in the context of the prostate.
B8.Summary.
What I have tried to do above, is to:
-show that sugar does not initiate cancer or accelerate its growth
-establish a path: carbohydrate → glucose → insulin, a PCa growth factor
-& a path: carbohydrate → glucose → triglycerides → prostatic visceral fat, a PCa stimulant
What can be done to control glucose? It’s actually quite simple. The Mediterranean diet is widely considered to be so heart-healthy that many men assume it to be low-fat. Au contraire! As much as 40% of calories come from fat.
Dr. Charles Myers has complained that new patients are often in more danger of death from CVD than from PCa. When asked what he ate for breakfast, a new patient might say: “I ate a healthy breakfast; juice, oatmeal & whole wheat toast without butter.” Sugar!
Dr. Myers promotes the Mediterranean diet & eats it himself. He is also a fan of Barry Sears.
Sears created the Zone diet many years ago. Each meal of the day should have carbohydrate, fat & protein in the same proportion. It sounds difficult but isn’t.
[B9] A last word on Sugar.
As mentioned before, sucrose (table sugar) is glucose & fructose in conjugate form. It must be broken apart during digestion before absorption.
For those who think honey is a better choice, it is mostly glucose & fructose, but not conjugated. The glucose is immediately available to the body. It does come with micronutrients, but at a steep price.
I doubt that fruit played a significant role in our evolution, but we are now encouraged to eat several portions every day. Given the ratio of sugar to nutrients, that is dubious advice.
I suppose that many associate fruit sugar with fructose, & assume that it is healthier than high-fructose corn syrup. Fructose is fructose, & fruit comes with other sugars too. There is often nearly as much unconjugated glucose as fructose.
Grapes are over 15% sugars, with almost half being glucose!
In contrast, strawberries are only 5% sugars – 2% glucose.
Fructose is processed to glucose by the liver, but the process is slow. It has long been used as a safe sweetener for diabetics. Fructose is not liver-friendly. Best to limit intake.
-Patrick
[B1] en.wikipedia.org/wiki/Otto_...
[B2a] mskcc.org/blog/no-sugar-no-...
[B2b] mayoclinic.org/diseases-con...
[B3a] en.wikipedia.org/wiki/Cellu...
[B3b] ncbi.nlm.nih.gov/pubmed/111...
[B3c] ncbi.nlm.nih.gov/pubmed/166...
[B3d] ncbi.nlm.nih.gov/pubmed/203...
[B4a] heart.org/HEARTORG/Conditio...
[B4bi] ncbi.nlm.nih.gov/pubmed/248...
[B4bii] ncbi.nlm.nih.gov/pubmed/216...
[B4c] en.wikipedia.org/wiki/Trigl...
[B4d] ncbi.nlm.nih.gov/pubmed/139...
[B5a] ncbi.nlm.nih.gov/pmc/articl...
[B5b] ncbi.nlm.nih.gov/pubmed/125...
[B5c] ncbi.nlm.nih.gov/pubmed/117...
[B5d] ncbi.nlm.nih.gov/pubmed/162...
[B6a] ncbi.nlm.nih.gov/pmc/articl...
[B6b] ncbi.nlm.nih.gov/pubmed/199...
