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lundi 10 février 2014


The Jakarta Post is an English Language newspaper published in Indonesia and as regional newspapers go it has less parochial and more of an international slant than Straits Times of Singapore or the rags that pass for Newspapers published in Kuala Lumpur. On a recent day when I was there, I was surprised to see the wide coverage, including International Affairs, Health, personal and public. And also there were delightful articles on Travel to this varied and exciting archipelago, I read about Anambas archipelago! It would be nice to go there indeed.
(Location of Anambas archipelago. I wondered whether they are part of the Natuna islands that my boat used to pass by when i was a school boy visiting Borneo?)

They had fully covered the recent cancer report published by WHO on the World Cancer day that falls on 4th February.
The gist of the report is that, like many other diseases now Cancer is also more prevalent in developing countries, Because of lack of treatment the mortality is much greater in less developed countries than the developing countries. I was surprised to learn that the incidence of cancer in Iran had dramatically risen; I wonder whether the western sanctions had anything to do with it? It is not a fantasy to think so, when Cuba was facing special period in the early 1990s, there was a spate of Optic Neuropathy, which could be related to the changes in the nutritional levels due to the economic collapse of the Soviet Union!

I wanted to write about Nutrition, Obesity and Cancer and how this relationship can be explained from a medical and anthropological point of view. There is a definite correlation between Obesity and Cancer and many scientists had dismissed it as being a relationship between diet and cancer.
A little behind the scenes research led me to some fascinating science.
It was two decades ago that young American scientists discovered an enzyme Phosphoinosotide Kinase (PI3K). At first its functions were less clear but soon it was realized that high levels of this enzyme correlated with malignant transformation of cells. It was also discovered that viruses that cause cancer in animals do so by turning on this enzyme. The same enzyme is activated by Growth Factors (like EGF, PDGF) and it was no surprise that Insulin also turned this enzyme on.
(A light suddenly went on my head: in my research into the association between Insulin and Acanthosis Nigricans, the dark marking in the back of the neck of people who have high levels of Insulin, was thought to be due to its action as a IGF).
By 1990, it was established that virtually everything that Insulin id required the activation of this PI3K. By studying earlier life forms such as flies and worms, the ancient pathways of ageing was well preserved but the IGP pathway of PI3K activation was less so.
The researchers felt that PI3K and its product PIP3 were originally involved to mediate Insulin/IGF-1 signalling and to control nutrient uptake-particularly glucose uptake in response to feeding and distribute it to the appropriate tissues for the organism to grow.
You would hear very often these days that not all calories are the same. (Nutritionists and doctors are very calorie-centric, talk about total calories without paying attention to what make up those calories). Also Fructose has been in the news lately, as the ubiquitous High Fructose Corn Syrup has proven to be a villain in this nutritional drama. Fructose and Glucose have the same amount of calories per gram. The table sugar or sucrose contains equal amounts of Fructose and Sucrose. But they follow different pathways in the body. In the Liver, fructose and glucose are metabolized differently. Fructose is converted into Fructose 1 Phosphate where as the fate of Glucose is Glucose 6 Phosphate. Glucose 6 Phosphate is acted on by PFK (phosphofructokinase), which is the gatekeeper enzyme for Glycolysis, the breakdown of the Glucose, to be storied as Glycogen, when it is not needed for energy. Its cousin Fructose 1 Phosphate acts as substrate for the action of Aldolase, which bypasses the gatekeeper PFK, then is converted directly into Fatty Acids.
The importance of these findings are that, no matter how much you have eaten, you will still make more fat if you eat more Fructose. Liver immediately converts Fructose into Fat while Glucose stays for a while in the blood stream.
(It is interesting to note that among the American Indians, this floating glucose can be lowered by exercise, even just a few minutes of it.)
(In a paper published in 1959, it was shown that
Acute Exercise lowers plasma Free Fatty Acids concentration. There is a significant rise in the FFA concentration immediately after exercise)
(So exercising to neutralize what you eat would need to take into consideration the quality of your food, what it contains rather than just calories!)
Brain needs Glucose; as it cannot use Fructose, neither can the muscles. Fructose is stored as Fat in the muscles.
You would get hungrier if you eat Fructose instead of Glucose. Many a times I have heard people complain that after a carbohydrate meal they feel hungrier than before!
In an exciting explanation, Dr Lewis Cantley the scientist discoverer of PI3K explains this unique evolution of the Fructose metabolism in the liver.
He writes:
You might ask - well why did we evolve such a complicated
System? Why does only the liver feed fructose
straight into fat? I think it’s quite clear why this happens.
We have a symbiotic relationship with plants. Plants
want to spread their seeds around, so they surround
them with fructose. High-fructose material surrounding
the seeds gets us and other animals to eat them and this
craving of fructose makes us eat them a lot and we end
up carrying their seeds around and spreading them. But
at the same time, it gives us an advantage because those
fruits ripen just at the end of the growing season, which
generally means, in almost all environments, that you’re
not going to have much to eat over the next few months.
So the best way to survive is to convert everything you
eat at that time into fat. That is the long-term storage
mechanism that allows you to survive until the next
growing season. That’s why fructose was spectacular for
us 10,000 years ago, getting us through these famines
that we faced every year. But today we don’t have famines
and so we just get fat.
Many in the Nutrition field as well as Anthropologists are well aware of Dr Neel’s theory of the Thrifty Gene, 1962. I am a firm believer in that since I have seen its action in the body metabolism of the Indigenous people when they become sedentary and adopt a food that is not theirs. (Paradoxically, Indonesians and Malaysians are now eating food that is not theirs: KFC, McDO, Pizza Hut etc.!)

Since the word Fructose conjures up a vision of Fruits, which contain Fructose, many a time patients ask: should we stop eating Fruits because of this scare about Fructose?
I can easily satisfy their curiosity by pointing out that one bushel of apples have as much Fructose as a 40 oz. bottle of Coca Cola or other soft drink! (One litre bottle). Fruits have other wonderful nutrients where as soft drinks have none!
To appeal to the consumer, to promote drinks as Light or Diet, artificial sweeteners are added. I have always been against artificial sweeteners. It gives you a sensation of sweetness, but brain craves sugar in its glucose form. Brain sees a disconnection between the taste of the sweeteners and the actual amount of glucose coming into the brain. As brain craves Glucose, consuming a lot of artificial sweeteners would lead a person to binge eat to satisfy their brains.
How can you stop it?
Stop eating Fructose as a chemical added to your food and throw away that artificial sweetener, whether it is Splenda or Stevia from the Amazonian leaves!
Certainly, I have seen that among my patients one of the difficulties of their loosing weight is the desire to binge eat. Don't call it an “Eating Disorder”; it is a chemically created socially manipulated metabolic stimulus!
What are the implications of this for the health of ordinary human beings?
Mice who are genetically modified so that they cannot metabolize Fructose tend to be healthier!
Say NO to Fructose except when it comes in Fruits! No to Glucose Syrup (a clever marketing technique!). Glucose syrup has only 10-45 % Glucose! Brown Rice Syrup adopted by many health gurus has only 3% glucose and the rest is in other forms of sugar, maltose.
We have some idea now that how our modern nutrition has caused us to have Fatty Liver, elevated cholesterol, obesity, Diabetes and other common chronic diseases.
What is the relationship between cancer and Nutrition? Is it a direct effect or mediated through Obesity?
A number of cancers are related to Obesity
Breast cancer after menopause
Adenocarcinoma of the Oesophagus (the garden variety is squamous cell carcinoma which is related to smoking and drinking)
Cancer of the Kidney
Colorectal cancers
Cancer of the endometrium
As you can see the hormone sensitive cancers are on the rise.
One can say that the higher incidence of cancer among the Overweight and Obese people may be attributed to
1.   The chemical and artificial food ingredients they are ingesting
2. The hormonal changes brought on by just increased adiposity
Body Mass Index (a measure of overweight and obesity) is related circulating oestrogen levels. The adipose tissue converts circulating androgens into oestrogens.
Increased Insulin levels as seen in overweight and obese people has a negative effect on Sex Hormone Binding Globulin, which then creates a milieu of, increased free oestrogen and free androgen. Oestrogen does activate the PI3K pathway and the malignant transformation
So we have come around in a circle in this article.
The exciting discovery of PI3K, the nutrition and malignant transformation paradigm and the role of insulin in it, as well as other hormones, all of this can culminate in obesity and overweight as well as malignant transformation of cells.

PS from a very selfish point of view you can see what a visit to Indonesia can trigger in your mind.
This article dedicated to my Indonesian host, HP, who is extremely exercise conscious and eats good food each and every meal. It is a great paradox that it is easier to eat well and healthier in poorer countries than richer countries and that when the people in poorer countries adopt the poor diet of the westerners they succumb to all sort of diseases.