Stay Hungry

For everything there is a season. There is a time to feast, a time to go hungry, and a time to consider your options. I propose to start at with an hors d’ouevre, meander through the middle course and finish with a just desert.

Fade up from red to reveal a foetus bathing in amniotic fluid, its umbilical cord disappearing out of frame. 

—Narrator: ‘The start of life, or close enough. The child gets its nutrition from the mother. But who does she get it from?’

Cut to shot of hospital lobby with a McDonalds outlet (ie Jackson Memorial Hospital in Miami).

—Narrator: ‘Not such a good start, then. This mother loves junk foods, just as well since it’s all she can afford. Her mother used to cook but this Gen Z mum doesn’t have time for that. She started eating ultra-processed while she was at high school and college and acquired a taste for it. Not surprising. It’s cheap, it’s everywhere and it is near-addictive.’

Cut to a delivery ward. A near-term woman lies on the bed with hospital staff around her.

—Narrator: ‘And it will cast a long shadow over this new life, from childhood to old age and death. Which will likely come sooner than nature intended.’

Curtains are pulled across the lens / wipe to reveal a researcher sitting in front of a computer screen, scrolling through a PubMed page. Or at a lab bench, if that’s your preferred stereotype.

—-Narrator: ‘There is so much evidence now that what the mother – and to a small extent the father – eats, will impact on the child’s health- and life-span. The story starts two decades ago, when Hales and Barker first proposed the thrifty phenotype hypothesis (1-3) …

If a foetus cannot obtain all it needs for healthy growth, the inherent drive for life leads it to alter its metabolism and the structure of many of its organs in order to survive. Most of these changes appear to be permanent, and what allowed short-term survival becomes a long-term handicap. These children will grow old enough to breed, so our selfish genes win out. But there is a heavy cost. 

Low birth weight babies which are still underweight at one year have abnormal glucose tolerance, a high risk of type 2 diabetes and the highest mortality rates from ischaemic heart disease (2, 3). These findings have been replicated by many other researchers (ie 4-10). 

Pre-clinical studies have shown that foetal dysnutrition creates long-term changes in the structure and functioning of inter alia the pancreas (11-13), muscle (14, 15) and adipose tissue (16). These changes are largely driven by the mother’s glucocorticoid stress hormones (17, 18). They all predispose to insulin resistance, they match the clinical findings almost exactly, and they make sense.

If a foetus is starved of nutrition, it will instruct peripheral tissues via epigenetic mechanisms to turn away glucose (and other nutrients) in order to divert them for structures essential for short-term survival, such as the brain. This lays the foundations for diabetes in later life, and may still not be enough to protect the brain if maternal nutrition is bad enough. 

The role of dysnutrition and chronic inflammation during pregnancy in causing spectrum disorders in children was discussed in a previous post, ‘Inflamed in the Membrane’. A recent review shows that maternal stress and nutrient restriction during pregnancy create epigenetic and neuroanatomical changes in the developing brain, which will probably be the single most important factor in determining mental ability (19, 20) and health for the rest of that child’s life (21, 22).

Going back to the problems of insulin resistance, prevention is – as always – better than cure. Too often, sadly, there is no cure. If the low birth-weight baby is over-fed and there is rapid ‘catch up’ weight gain, the risks of diabetes, heart disease and mortality increase further (23-27). 

With nutrition, timing is everything; but so is the happy medium, because at the other end of the scale, heavy babies have problems of their own. And their numbers are increasing (28), because overweight mothers tend to have over-weight babies (29).

The data are not entirely consistent but it is likely that over-weight babies will grow up to experience an increased risk of obesity (30), type 2 diabetes (29-32), heart failure (33), osteosarcoma (34) and mortality (35).

Heavy-weight babies are victims of a different kind of malnutrition, where a mother’s diet and/or weight have created long-term or gestational diabetes. Her raised blood sugar levels cross the placenta but her insulin cannot, so the foetus must pump out its own insulin to keep its glucose levels somewhat under control. Insulin is a potent growth factor in foetal life, hence the bigger babies. These will go on to become more obese, more diabetic and more disease-prone adults; and to have, in turn, more heavy babies. 

This is exactly the same pattern seen in lab rats fed on junk food diets (ie 36-39). Their overweight and diseased offspring display a distinct preference for the same junk food diet that sickened their mothers (40, 41), become obese (42) and go on to develop the same kind of fatty liver disease (43) that now affects a quarter of the world’s population (44). A diet with an abnormally high glycemic load, insufficient prebiotic fiber and plenty of trans fats (45) will do the trick.

Would-be fathers should cut down on junk foods too.

Paternal pre-conceptual diet is known to affect sperm quality (ie 46), and emerging evidence shows that it plays an epigenetic role in shaping the infant’s long-term health prospects also (ie 47, 48).

Our children have become lab rats in a vicious cycle driven by a food industry which is not only killing us in droves but also condemning future generations to ever-increasing degenerative disease, mental illness, accelerated ageing (49-62) and therefore early death. 

Anyone old enough to read this, however, should just say no. At least, intermittently. A multinational research group (mostly LA and Milan but also Turin, Genoa and Palermo, with contributions from Berlin and London), has been examining the health benefits of intermittent fasting – and it looks as if this may be an answer to most of the problems listed above.

Repeated water-only fasting periods of 48 hours exert highly protective effects against diabetes cancer, heart disease and neuro-degenerative disease in pre-clinical models (ie 63-67). 2-day total fasts are too difficult for most humans, however, so the team developed an easier format which they termed the Fasting Mimicking Diet (FMD.

The FMD is a very low calorie / low protein diet that is consumed for cycles of 4 consecutive days once a fortnight, or for five consecutive days once a month. 

This dietary approach is enough to trick the body into a fasting state and promote multi-systems regeneration, enhanced cognitive performance and health-span (68). It also promotes bone density and hippocampal regeneration in older animals (68, 69), reduces autoimmunity, restores a healthy microbiome and gastrointestinal system (69, 70) and protects against cancer (68, 71). It seems to be as effective as the long-term calorie restriction practised by obsessives.

If you’re going to try intermittent fasting, timing is critical. A minimum of 18 hours/day, with the clock starting in the late afternoon or early evening is best. Our adipose tissue has its own circadian rhythm, and goes to sleep after dark (72). This is why insulin resistance increases at night, why late-night eating fuels weight gain (73, 74) and why eating within 2 hours of going to bed is an independent risk factor for NAFLD (75). (See posts Night and Day, Foie Gras).

But what, you might ask, about protein?

While high protein diets are well tolerated in children and young adults, low protein diets are probably better for older adults and are generally associated with longer health- and life-span (ie 76, 77).

This might be because older adults are more likely to have impaired liver and/or kidney disease; or to have a cancer in situ which could be driven by high IGF1 into clinical cancer (77).

Reduce protein intakes and you reduce IGF1 (78). However, in the elderly IGF1 levels are already low, which tends to make it difficult to maintain muscle mass. Higher protein intakes may therefore play a role in warding off sarcopenia (77), and in cancer cases are generally recommended to reduce wasting.

If you are of pensionable age, therefore, you should aim to be in the Goldilocks zone. Not too much protein, and not too little either.

If you are going to try a low calorie and low protein diet, the quality and source of the proteins you eat becomes more important. There is epidemiological and other evidence that plant-derived proteins may be healthier in older age than animal-derived proteins (ie 77, 79); but this too is a complex issue. 

Some amino acids are more equal than others when it comes to triggering the body’s nutrient-sensing pathways, and some researchers believe that plant proteins may score here due to their generally lower methionine levels (ie 80). I am not so sure; rice is an excellent source of methionine, and the proteins in animal and in combined plant dishes (ie rice and beans) contain very similar arrays of amino acids. I think we have to look not only the source of the protein but also how it is cooked, and the presence or absence of other dietary components. 

Meats are more likely than plant foods to be cooked at high temperatures, boosting the production of carcinogens (81); and they do not contain dietary fibre.

Prebiotic fibres are exclusively found in plant foods, and have a large positive impact on health and life expectancy (ie 82). If you are going to opt for a diet that is low in protein and want that protein to be good quality and combined with prebiotics, the pre-transitional rice and peas (Caribbean), rice and beans (South America and Asia) or falafel in pitta (the Middle East) are three delicious ways to go.

If you add the Health Protocol, which will reduce neuro-inflammation and therefore IKKβ/NF-κB/GnRH signalling in the hypothalamus (83, 84), you should slow the biological clock even more.

It is effectively impossible to run the kinds of clinical trials that would be required to provide proof of concept, but perhaps we don’t need to. We could play war games instead.

During WW1, the Danish population was forced to reduce calorie consumption for 2 years, but maintained adequate consumption of whole-grain cereals, vegetables and milk. This happy circumstance led to a 34% reduction in death rates (85). During WW2, Oslo citizens experienced enforced calorie reduction of 20% without malnutrition for 4 years, and mortality fell by a similar amount (85).

Death rates falling during war obviously only applies to non-combatants, and are unlikely to occur in WW3 which, if Joe DiMentia has his wag the dog moment, will place all of us in the front line. Notwithstanding, they provide compelling evidence for the virtues of hara hachi bun me, a Confucian teaching that suggests you should leave the table still hungry, hormetic and therefore autophagic (86).

Next week. Sweetening the pot; the health benefits of rare sugars.

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