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.
