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There’s firm evidence in animal studies that lower levels of
IGF-1 can lead to better health and longer life expectancy: mice on a diet of
either continuous calorie restriction or intermittent calorie restriction have
been shown to live 40% longer than mice fed a normal diet: that would be the
equivalent of a person living to 120 or more!

Indeed, a recent report also suggests that a hormone that
blocks the action of IGF-1 might in future offer some of the longevity benefits
of fasting or calorie restriction – without having to fast! A group of mice
were genetically engineered to produce constant supplies of a hormone usually
produced during fasting, FGF21. The experiment extended their lifespan by a
third, although
fertility and bone density where affected (for more detail about all these
studies, refer to the links section at the back of the book).

The
curious case of the people ‘immune’ to cancer

Of
course, we need to be wary of assuming that what works in mice will work in the
same way for us. One clue comes from a rare
human
genetic condition
known as Laron syndrome, where very low levels of IGF-1 are produced. People
with the mutation don’t grow very tall, but the lack of the hormone also has
very strong protective effects against cancer and diabetes. Professor Longo
from the University of Southern California – the same guy who gave us the car
analogy above - monitored 99 people with the condition in Ecuador with
astonishing results.

To date, they’ve now been followed for twenty-four years,
and none of them have developed diabetes, and only one has been diagnosed with
non-fatal cancer. Yet 5% of their neighbours – with similar diets and lifestyles
- have been diagnosed with diabetes, and 17% had cancer diagnosed during that
same period. Overall, the Laron syndrome group didn’t live longer, but that
may be down to the high number of accidents caused by being smaller.

One pointer towards the possible protective effects of
low-levels of IGF-1 came when the scientists studied blood serum from those
with the Laron mutation under the microscope. Cells suffered less DNA damage
than ‘normal’ blood cells from non Laron patients when they were exposed to a
toxin. Yet when the scientists added IGF-1 – that protection disappeared.

Food
and IGF-1

So
if IGF-1 is a contributor to DNA damage – the kind we talked about when we were
discussing Free Radicals and Oxidative stress - then what happens when we eat
less and consequently produce less IGF-1?

It seems that as levels of the hormone drop, the body goes
into the repair mode  we mentioned before. This amazing process is one we can
trace right back to the way our ancestors lived.

Their lives involved the most extreme version of ‘fasting’
and ‘feasting’ – Tina put it so clearly when she wrote to update her progress
since she’s been doing 5:2.

If you think about it, it's
the most natural way to eat and probably how our cavemen ancestors would have
survived. They'd have hunted an animal, eaten their kill, and may not have
caught another for a few days so would have eaten much fewer calories until
their next catch.

Tina, 49

Our
bodies adapted to such dramatic variations in food intake very efficiently –
but as I said in my introduction, it means they are focused on laying down fat
stores, which works less well for us in times of permanent plenty. So this way
of eating simulates the same lifestyle – and scientists have focused on the
actions of one particular gene that is key to the repair processes.

The
SIRT1 Gene – Gene Genius of anti-ageing?

That
gene is called the SIRT1 gene and  produces a protein, Sirtuin (
silent
mating type information regulation 2 homolog
: don’t worry, there won’t be a
test at the end). Calorie restriction and fasting seems to activate the gene,
with life-extending and anti-ageing effects.

It certainly does the trick for yeast and worms. Having
extra copies of this gene extends their lifespans.

In human-focused research, there’s been attention paid to
the effect of calorie restriction in activating the gene, and all the ‘repair
mode’ benefits we’ve been discussing in this chapter.

The theory goes that Sirtuin may play a part in
regulating/improving the processes we’ve discussed above, including apoptosis
(regulated cell death), reducing damage by ‘free radicals’ and also reducing
what’s known as inflammatory response. That’s where the body tries to protect
itself from infection – it works well when you have a cut or a minor infection,
and various infection-fighting cells cause inflammation including redness and
swelling as they race to the location to fight the infection. But it’s not good
news when your body overall stays in this inflamed state – in fact, it’s
thought chronic inflammation might be responsible for many medical conditions,
including cancers, heart disease and arthritis.

So a reduction in inflammation triggered by SIRT1 may be
responsible for many of the benefits seen in animals and humans – and it can be
activated by calorie restriction, including 5:2 and ADF diets. Further
research is ongoing into this – and into the possibility that you can also give
your SIRT1 gene a boot up the backside with… red wine?

The
Wine Connection

The
skin and pips of grapes contain a molecule called resveratrol – and some
scientists believe this might partly explain the ‘French Paradox’ – where
studies have shown French citizens live longer than other Western Europeans,
despite diets high in fat.

But before you crack open the vin rouge, I have to tell you
that the research is not conclusive and is ongoing – billions of dollars are
being spent trying to use this knowledge to develop life-extending treatments.
Yet the role of the resveratrol – and the SIRT1 gene in general - in increasing
lifespans is still controversial.

Uncertainties
and motivation

The
precise mechanisms of SIRT1, resveratrol and IGF-1 in the fasting process are
still unclear, but there are numerous studies showing the potential beneficial
effects of ADF and calorie restriction on different medical conditions. 

Research in this area is ongoing, but for me (and for most
of the scientists involved), there’s enough evidence from different sources to convince
that the 5:2 (or 4:2, 6:1 or ADF) life is the way forward.

In the next section, I’ll summarise some of the most
exciting medical research – I’ve found this very motivating to flick through if
the hunger pangs strike! Remember there are links to all the research in the
section at the back, so you can follow up the areas that are of most interest
to you.

Medical
research on specific conditions

Much
of the evidence at this stage comes from animal studies, because human
lifespans are so much longer and therefore the studies take longer too. So
where humans have tried ADF or Calorie Restricted Diets, the effects are often
measured by blood tests that show chemical ‘markers.’ These indicate  the
likelihood of developing certain diseases, e.g. insulin sensitivity for
diabetes, LDL and HDL cholesterol for heart disease.

The
more this area of research grows, the more long-term information about the
real-time results in human subjects should be available.

For
an excellent overview of some of the best research in the field, Dr Krista
Varady – who featured in the ‘Horizon’ programme – and Dr Marc Hellerstein put
together a review of studies in 2007 – there’s a link in the resources section.
 

Cancer

In
animal trials, there are signs that ADF (and intermittent calorie restriction)
has inhibited the growth of certain cancer cells, and improved response to
anti-cancer therapy.

Meanwhile the Genesis Breast Cancer Prevention Centre
(
genesisuk.org
) in Manchester has been measuring the effects of an intermittent
calorie restriction diet, similar to the 5:2 diet, in women with a high risk of
developing the disease.

Because excess weight is often associated with an increased
risk of breast cancer, lowering weight can reduce the risk by up to 40%. But
this form of dieting might offer extra benefits at cellular level.

In one study, the intermittent fasters lost nearly twice as
much weight as the ‘daily dieters and also showed greater improvements in ‘insulin
sensitivity’ – which is an excellent result in terms of diabetes prevention
(see more about this later in the chapter).

The BRRIDE (Breast Risk Reduction Intermittent Diet Evaluation)
study has analysed breast and body tissues to see if the diet has made
changes to how the genes are behaving. The hope is that that a diet of 1,800
calories five days a week, and 600 calories two days a week, may reduce the
activity of the SCD gene which is thought to be a factor in the development of
breast cancer.

As I’ve mentioned before, most of my female relatives on my
mother’s side of the family have had breast cancer diagnoses. Apart from my
regular mammograms, I’ve felt powerless in the face of this history. Until now
– the evidence may not yet be there in black and white but I await the outcome
of this study with particularly keen interest. Dr Michelle Harvie and her
Genesis team have also written a new book summarising their dietary advice –
there are full details of this, and all the research in this chapter, in the
Resources section at the end of the book.

Prevention is – obviously – better than cure, but there are
also indications from research in animals, and some limited studies of humans,
that fasting at the right time can make chemotherapy treatment easier to
tolerate, and perhaps more successful. One theory is that fasting puts the
body’s healthy cells into the slower-paced repair mode, but the ‘rogue’ cancer
cells are still proliferating. So the healthy cells are less vulnerable to the
toxic effects of chemotherapy, while the malignant cells which the chemo is
targeting, are attacked more effectively. Further research in this area is
ongoing as I write though any decisions about fasting before such treatment
must be discussed with your oncology team.

Heart
Disease

Cardiovascular
disease affects almost every family – it’s the leading cause of death in the UK
and world-wide. The term is used more broadly than you might think, to include
high blood pressure, heart attacks and also strokes, so it’s understandable
that it’s a major concern.

It’s
also one of the areas of medicine that researchers are focusing on when they’re
assessing the benefits of fasting diets.

In a range of animal studies, rodents saw a decrease in
blood pressure, heart rate and cardiovascular disease risk indicators when they
were put on ADF regimes. In another experiment on rats, the damage caused when
a heart attack was deliberately induced was less in those being fed ADF than
normal diets.

Krista Varady and her team at the University of Illinois
have led the research with human subjects in this field. She’s run a number of
studies (find more details in the resources section), which have shown that
intermittent fasting is effective in helping people lose weight – and also
appears to result in less loss of muscle than conventional calorie-controlled
diet regimes. The important results for cardiovascular health were the
reduction in levels of LDL (or ‘bad’) cholesterol and triglycerides in the
blood, as did blood pressure readings in one study.

In our group of 5:2 dieters, six have already reported lower
blood pressure readings and several more have seen lower levels of ‘bad’
cholesterol.

Type
2 Diabetes

I’ve
seen first-hand how Type 2 (or ‘adult onset’) diabetes is not the minor
inconvenience many people assume it to be. The condition can cause cardiovascular
problems, kidney disease, damage to the retina, nerve problems and damage to
circulation in the legs and feet that can even lead to amputation.

Type
2 Diabetes is increasing dramatically in adults right across the world, but more
children and young people are being diagnosed with it, too, mainly due to the
increase in obesity levels in this age group. The implications for the health
of individuals – and the cost for health care – are frightening.

Type 2 diabetes develops when the body becomes less
efficient at dealing with the sugars that we consume through food. When we eat,
much of the food is turned into simple sugars, to provide energy to the cells.
The hormone insulin, produced by the pancreas, helps to regulate blood sugar
levels– too much is dangerous so insulin sends an instruction to the cells to
take in more glucose, so the levels in the blood will drop.

The problem comes when the pancreas stops producing enough
insulin or when the cells stop being as responsive or sensitive as they should
be to the hormone. This happens most frequently in people who are overweight,
because excess weight makes it harder for the body to regulate blood sugar, but
can also happen in those of normal weight.

 For many years, dieting wisdom has favoured ‘grazing’ as a
way of keeping blood sugar stable. The idea is that you snack between meals, so
your blood sugar levels are never allowed to drop (a drop will send hunger
signals to the brain, prompting you to eat more). This idea can work if you eat
healthy food in small portions – but as we’ve seen, the temptations to snack on
high-fat and sugar foods are great. Which means you put on weight
and
your
pancreas has to work overtime.

It seems to make sense to me, as a non-scientist, that
reducing the number of sugar/insulin spikes you experience by eating less often
during the day would make it easier to regulate blood sugar levels. It can also
affect levels of fat, because insulin is
lipogenic.
While insulin is
circulating, your body lays down fat stores, instead of burning fat – another
reason why dieters would want to reduce too many spikes.