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Table 1 Public health responses to the composite unifying theory for decreasing metabolic syndrome & obesity related co-morbidities

From: Past and future corollaries of theories on causes of metabolic syndrome and obesity related co-morbidities part 2: a composite unifying theory review of human-specific co-adaptations to brain energy consumption

Type & putative reason

Mechanisms

Effects on human form & function subsequent relationship to disease

Public Health Policy & Action

Expanded Cortico-Limbic-Striatal System (human specific/ adapted) [Increased Energy Uptake].

• The cortico-limbic-striatal system is present in mammals (palaeo-mammalian brain derived from reptilian elements). The system ensures behaviours follow basic drives for food energy, sex, power etc. It controls planning & motor co-ordination, with motivation enhanced by significant neural reward in humans

• Sociological literature has dealt with the huge disparities in power between individuals in populations, usually to acquire or manage resources such as food production & human labour. This is typical of human society, however ‘power addiction’ as it relates to public health, is rarely discussed.

• Public health is about promoting & ensuring healthy environments & the rights of all to health. Basics, such as nutritional & safe food, remain pivotal. In practice, often indirectly, it involves defending those with limited resources for healthy lives from those who have (expropriated) more resources. Governments, which largely fund public health programmes & should have the same aims as public health, are highly influenced by profitable industrial lobbies. Lobbyists & politicians’ jobs are all about power, so any ‘addiction to power’ is an issue for public health. Ethical considerations & scientific evidence may not always shape laws which politicians devise & pass. Big Food, a typical profiteering industry, has a powerful, multinational lobby; whole food producers are the converse.

• Reward is determined by dopamine function, & mediated by many endogenous & exogenous neurotransmitters such as opiates, cannabinoids etc. by direct stimulation or by items/situations of learned salience (initially pleasure)

• Highly driven/perseveration behaviours with feed -forward reward systems may have transferred to many pursuits, including discovery, invention & technology (often designed to increase energy acquisition), gaming, gambling, & systems of power over others

• Public health workers have an number of options, which could include to a) become educated in tertiary institutions with a high degree of academic freedom b) work out an ethical code with(in) which to work c) critique all research & studies for adherence to sound hypotheses & methods d) have a working knowledge of new basic science developments, changes in macroeconomic trends & effects of technology e) collaborate with & harness the support of the many civil society groups

• In humans, there is a large expansion of this system in form & function – with the dopamine transporter showing recent rapid evolution, high degrees of variation in genetic variability & epigenetic responses.

• ‘Reward hypo-function’ requires more of the ‘stimulant’ in order to function; enjoyment is often no longer present

• Public health system staff & policy makers will face resistance from themselves personally – a) why should they personally cut down on refined & appetising foods, b) why should they resist a main source of income as much research is carefully backed by food processors/marketeers, c) why should they fight their colleagues in nutritional, supplement, pharmaceutical, food & agribusiness all for a theory.

• Increases in &/or repeat seeking behaviours can be extreme (perseveration, obsessive- compulsion)

• Obsessive compulsive disorders commonly follow, & highly cued, addiction ‘habits’ develop.

• Public health can support dealing with addiction as biology, not buying into blame of sufferers with statements on ‘individual responsibility’ – which certainly does not help children

• Addiction can occur or restart in ‘permissive’ environments, or when individuals are under stress

• ‘Refined food addiction’, loss of control, binge eating over-palatable food, distress, guilt, depression, is so strong that obesity commonly supervenes, in spite of marked social disapproval & derision

• Public health workers on the ground & primary care health professionals, need support for early addiction detection & help with addiction therapies:- non-judgemental counselling, abstinence from certain foods, replacing the refined high energy food addiction with healthy foods & habits, & use of safe anti-addiction medication

• Addiction relies on cues, & habit formation: can be extreme (obsessive-compulsive perseveration)

• Obsessive compulsive disorders - includes anorexia nervosa, bulimia & many others

• Public health messages are frequently low impact, non-productive, admonishment of families’ behaviour & composed of soft, biologically outdated lifestyle advice. Public health workers could work to understand how not to buy into manipulative messages in the guise of ‘social marketing’. These are part of the tactics of Big Industry, to influence ‘media messages’ & normalise addictive items to populations. Such messages reassure people that their behaviour does not need much change; certainly not stopping. Messages such as ‘just having these foods as part of a balanced diet’ or, with respect to alcohol, ‘cut down on drinking’ are counterproductive for people with addiction.

• Addiction to power is little discussed in these terms, but probably stems from in same part of brain

• Addiction arises when power & technology systems make salient items easy to attain, & promise rewards of feeling better

• Public Health workers need to be aware of being steered into working with industry or having industry provide funds, especially to study industry- beneficial or deleterious issues. Governments tend to prefer to fund public health research on neutral epidemiology of illness rather than psychosocial issues associated with societal disparity. Public funding is rarely enough. Better designed, prospective preventative, positive role modelling community studies are needed.

 

• Loss of control over items/situation, leads to neglect of healthy & normal behaviours, such as healthy eating

• Public health could support & work with civil society groups in a mutually beneficial way, & possibly consider ‘crowd funding’ to get projects going.

 

• The dopaminergic system (as opposed to the serotonergic) is not ‘linked’ to logical/cognitive part of brain; talking individuals out of addiction feelings is not successful. Non-judgemental help to understand what addictions are, how rules around behaviours have to be made & ‘policing’ them, all need external input & support.

• Public Health staff need to keep trying to ensure advocacy & regulation to prevent public health damage from addiction & exploitation. Regulating where alcohol is sold & what food is available in schools, are derived strategies learned from tobacco control.

  

• Public Health staff should work to prevent Big Food/Alcohol/ Tobacco, Energy, transport industries lobbying with gifts to regulators. They should ensure totally transparent dealings with governments, & cessation of large direct & indirect public subsidies made to such industries.

Omnivory (human adapted) [Increased Energy Uptake].

• Omnivory increases energy by exploiting high energy/protein/nutrient animal tissue –lean (mostly muscle), fat (plus marrow, brain) offal (liver, kidney, & other). Omnivory continues use of (seasonal) ripe fruit with sugars, oil seeds (note high-starch foods were rare in pre-agricultural times).

• Wide varieties of plant & animal food were consumed & experienced by early humans, & gradually became required nutrients.

• Farming should be mixed, with a much higher ratio of plant protein/micronutrient rich food to plant starches, sugars & oils (the latter grown for industrial refinement).

  

• More animals & fish can be grown on mixed farms using organic waste such as carp in farm sludge ponds, & pigs in paddocks, geared to modest-sized humane & free range animal production. This yields multiple traditional products such as wool, leather, dairy & meat as well as providing omega-3, oil fish & other novel biodegradable products.

  

• Fermented food introduces more protein/nutrient density (from the microbes) & less energy, but alcohol content needs controlling. Fermented food may decrease levels of (saccharide) prebiotics, for those seeking to control gut distension as in irritable bowel syndrome.

Technology - (cooking, agriculture, mechanisation, research, computer use) [Increased Energy Uptake]

• Cooking softens /gelatinises protein, kills pathogens, improves food utility

• Publically subsidised large ‘high-chemo/tech’, monocultural agri-business farming ruins ecologies, depletes environments & foods plus adds many man-made xenobiotics – all decreasing NRF2 function

• Public Health staff need to work hard with governments to establish programmes of health system & self critiques, & listen to ideas on public health issues from the public, (other) theoreticians, scientists & systems modellers from various disciplines.

Health Food = naturally preserved from fresh, eg slow cooking, drying, freezing salting, pickling in vinegar/oil, sealing (bottling, tinning) keep many useful nutrients. Unhealthy Food = processing by refining, applying excessive mechanical & thermal pressure (& charring, inducing deleterious chemical /Maillard reactions eg advanced glycation end products), extraction with chemicals & inserting anti-nutrient chemicals which damages or poisons, plus eliminates many useful nutrients, in food whilst leaving extremely low ratios of micronutrients: macronutrients.

• Supermarkets & 'fast food' chains tend to be multinational oligopolies, with ‘units on a conveyer belt’ management systems, including inflexible controlling contracts with growers & workers, minimal community involvement

• Public health systems must look at obvious & scientific evidence of environmental/ecological damage, & lack of sustainability of (expansion in) food energy agribusiness, use of pesticides, antibiotics, propping up unstable mono-cultures that will become blighted (kiwifruit, battery chicken, bees), & overuse use of non-sustainable materials that ‘fuel’ climate change as they affect nation’s health

• Much technology is designed to grow, refine, alter, store, transport & trade in high-energy foods.

• Food marketeers & their ‘high tech’ extensive advertising renders high processed food as the norm

• Public health scientists need to be up-to-date with studies of sustainable, mixed crop, ecological farming using smart methods eg computer technology, large scale composting, & advocate against destructive resource exploitation, such as clearing forest for palm oil & kernel monocultures, which are not required

 

• Agribusiness is promoted by those who control economies & is normalised in the media.

• Public health scientists need to know that metabolomics technology can be used to study food & body nutrient status & health. (see healthy food grading, below)

  

• Public health systems need to be in contact with those of other nations – as 1/2 world’s food is wasted not counting millions of tonnes of fat energy on human bodies. They should be publishing this fact & coordinating science to combat this

  

• Public health should step out of its comfort zone & engage theoreticians to assess new theory & re-analyse data already present, with (mathematical systems) modelling studies

  

• Public health physicians, workers & researchers need to scan the evidence closely for health benefits & blow the whistle on /not support or endorse vast public/private funding for research. Such funding is often for high tech ‘industry branding’, that does not clearly have an over-riding, primary health outcome.

  

• Simplistic mono-nutrient/supplement/drug product & genotype matching industries are not real science-evidence based & are not contributing to public health science.

Co-Option of Numerous Micronutrients to Modulate the Human NRF2 System (human adapted) [Increase Energy Efficiency]

• Theoretically, the human NRF2 is super energy efficient possibly initially to accommodate the brain’s use of energy. This is due to the modulation by numerous food micronutrients.

• A continuous dietary supply of high micronutrient food with the minimum xenobiotic load is the way of deferring degenerative diseases of all types. The development of ‘technology”, driven by the same cortico-limbic-striatal system, has skewed the food intake too far from the requirements of the NRF2 system. The two systems are no longer complimentary, with the former disrupting the function of the latter.

• Public health staff know there is something seriously wrong in the area of obesity, diabetes, CVD & cancer, that their public health messages are not working, & programmes are not getting management correct with respect to nutrition.

• What is known is that the abundant use of food micronutrients affords increases a very high level of metabolic protection

• Metabolically, the forager situation is ideal. With good environmental & social conditions & plenty of physical activity, maximum physical & socio-cognitive potential & longevity should be reached.

• Public health always needs theoretical, broadly educated scientists who understand biology to independently assess many disciplines that contribute to population health - including current anthropology, psychology & appropriate (cancer) science.

• The expanded cortico-limbic-striatal system causes craving of energy dense highly attractive food which leads to neglect of healthy whole food.

• With the above, & normal exposure to the natural environment, allergies, auto-immune & cancer rates should be decreased. Children with asthma & allergies may benefit from having pets.

• Public health scientists have enough evidence to acknowledge that degeneration +/- obesity occurs early with extreme low micronutrient to macronutrient ratio food, as seen in many westernised countries, & to take action with pregnant women, their babies, children & teenage years for the next generation.

• Oxidative Stress control, hyper-efficient cell maintenance, & repair, allows healthy longevity with minimal tumour development or degenerative change - unusual in modest sized mammal.

• Learning to eat tougher, tasty, highly varied & nutritious food is hijacked by over-palatable, processed, normalised food. Children, youth & their offspring are propelled towards inadequate nutrition & shorter, unhealthy lives.

• Public health scientists will now understand that the signs such as obesity enhanced polycystic ovary syndrome & teenage TIIDM, will occur earlier.

• Stable Replication - highly functioning immune cells in infection control, & dysplasia prevention.

• A high antioxidant diet allows slow growth means & high cytoprotection over a long life. It sets the scene for menopause. Without lifelong micronutrient rich food any inherent cell reserve is depleted at middle age.

• Public health systems really need to help the poor & ensure that increasing disparities already present between wealthy & poor are decreased – otherwise this is not public health

• Repair work undertaken by the NRF2 (eg removing oxidised lipoproteins preventing arterial plaque) uses plenty of energy, but is deferred due to lack of micronutrients.

• Lack of micronutrient dense food post-agriculture, with variable energy & variable protein led to starvation, stunting, vitamin deficiency disease & susceptibility to acute/chronic infection

• A related public health issue is increasing neurological disease

a) psychiatric diseases of attention deficit/ hyperactivity disorder & many learning & conduct (cognitive disorders) have relationships to suboptimal in utero, infant & childhood nutrition

b) it is known that prevention of MetS in middle age decreases Alzheimer’s disease. Luckily humans have a good repair mechanism in the well supplied NRF2 system. It is never too late to gain some benefit from increasing nutrition quality.

• Extra unoxidised lipid is stored firstly in subcutaneous safe adipose tissue, then forced into ectopic sites such as liver, locomotor & heart muscle, & other tissue.

• Man-made persistent toxins lead to death, sub-acute illness, chronic disease, CVD, neoplasia or cancer.

• Public health staff will need to understand that oxidative stress along with the supervention of a mal-activated immune system may be behind high rates of communicable acute infectious disease. A poorly fed host, chronically exposed to many chemicals, such as diabetic immune compromised individuals is then exposed to contaminated low nutrient, factory farmed meat – that food poisoning is a problem of compromised host & food. Chronic infections disease such as pulmonary tuberculosis is also higher in poorly fed populations

• The theory promotes the idea that the lack of adequate micronutrients in humans’ diets & excess xenobiotics is the cause of MetS. In recent decades dietary energy overload has occurred & MetS is now coupled with obesity. This malnutritive obesity or 'malnubesity' is epidemic.

  

• On increased consumption of a high micronutrient food diet by individuals who are obese, ectopic & central fat appears to be mobilised in order to contribute to overdue repair work throughout the body.

  

Nomad & Forager cultures (human adapted) [Increased metabolic/energy efficiency & Increased uptake]

• NRF2 exposure to wide variety of plant (& animal) foods with co-option of antioxidants & wide exposure to natural toxins & adaptation to managing them.

• Increasing exposure to large varieties of food gradually allowed the co-option of antioxidants & consequent energy efficiency & management of plant toxins.

• World public health policy should learn from nomadic, forager, so-called subsistence & local ‘low tech’, farming societies, & protect from deleterious ‘nutrition transition’ to westernised food patterns

  

• Such communities protect regional environmental & food resources for the world, & they need: their land to be protected from resource exploitation, remain little disturbed, to be encouraged to feed themselves whilst maintaining biological diversity & stocks

  

• If energy & protein aid is needed for displaced, war or natural disaster exposed peoples, high nutrient local herbs & spice supplementation should be encouraged, or these condiments added to the food aid.

  

• Local community gardeners should learn from low tech farmers working in other countries.

Other metabolic management mechanisms (hominoid/human specific) [Energy Efficiency]

• Humans have lost enzymes to synthesize vitamin C (an energy requiring process). Also vitamin C, a sugar based vitamin, yields energy. Vitamin C may inhibit fat production from fructose.

• Vitamin C in fruit (& probably other plant micronutrients, fibre, & other plant food eaten concurrently) inhibits fat deposition from fruit sugars.

• Public Health workers around the world, to their credit, are gradually gaining traction on advice, & in some areas regulation, to decrease sugar content of diets, especially fructose & sucrose in sugary drinks. This is an example of solid basic science evidence being brought into clinical & public health arenas.

• Uric acid (high levels in hominoid serum) is antioxidant but in high levels, especially in cells, pro-oxidant. Levels markedly increase on fructose & recently found, glucose (& ?starch) ingestion, & rapidly forms liver fat.

• Consumption of high fructose corn syrup, sucrose in sugary drinks, is a major problem for liver, muscle & general fat deposition. Refined starch may be similar.

• Public health is yet to navigate the processed food companies in order to bring the role of food micronutrients, the likely major determinants of health, to the fore. This needs doing as soon as possible. There is, plenty of evidence from Mediterranean diet studies.

• Vitamin D metabolism is related to prevention of central obesity, diabetes, CVD, infection & cancer.

• Vitamin D appears to be associated with obesity, & relates to glucose regulation, metabolism & immune function (especially skin infections & cancer prevention)

• Public Health messages & programmes need updating & integrating. Obese populations with MetS also usually have low vitamin D levels, especially with darkly pigmented skin, & those who live in crowded, poor housing estates, with few parks & work indoors. As bowel cancer is more common in these groups, & vitamin D can decrease incidence & they may need more careful sun exposure. This manoeuvre may have an overall greater benefit than restricting all ethnicities from sun exposure to prevent individuals with lightly pigmented skin from melanoma. People can understand a message on careful, non-burning sun exposure if based on their skin pigment when the issue is of biology not ethnicity. NB Recent Vitamin D & calcium supplements do not seem to be preventing the above, nor fractures, adequately. Graded real skin exposure to summer sun is needed

• High levels of antioxidants (superoxide dismutase) & fluxes of brain glutamate (metabolism of energy & neurotransmission) are present in humans.

• Rapid & efficient antioxidant activity is especially highly developed in the brain.

• Genetic-epigenetic changes are present in the high glucose consuming brain, however, the brain is able to metabolise ketones during starvation.

Expensive tissue trade off

   

a)Smaller, simpler gut but still specialised [Energy Conservation].

• The human intestine is a less specialised organ, with no foregut fermentation (no ruminant cellulose digestion), & modest protein fermentation. It is however, very flexible & adaptable

• Gut health itself, let alone the whole body, depends on food micronutrients & fibre (the latter which often carry minerals & vitamins) for normal metabolism & weight

• Public health can emphasise in its public campaigns that eating healthy diets with lots of natural whole food fibre & phytochemicals will keep the symptomatic bowel dysfunction (constipation & irritable bowl) rates in check

• With a high plant & whole food diet, beneficial Bacteriodetes microbes predominate. This is associated with better toxin & pathogen management, & normal weight & metabolic health. Appropriate micronutrients & energy are absorbed, but minimal microbial inflammatory particles. The converse is true with a low quality, energy dense diet, where Firmicutes predominate, & metaflammation may arise from plasma microbe particles & DNA.

• Gut motility depends on large groups of micronutrients & fibre. It is under recognised that vegetable and non starch seeds (such as nuts & flax/lin seed) fibre prevents slow bowel transit, constipation & haemorrhoids.

• Public health messages should stop spreading fear of normal environmental microbes/dirt/animal dander/etc ingested with low xenobiotic foods which stimulate normal gut & body immune development. Realistic, plausible, up-to-date science shows these immune stimulators reduce allergic disease eg asthma, & autoimmune diseases of Crohns & rheumatoid type which are already increased in those with MetS.

• The gut needs appropriate immune stimulation to reduce allergic & autoimmune diseases.

• Immune stimulation occurs by exposure & processing of variably noxious food, microbes, environmental particles & chemicals. Thus the body distinguishes pathogenic items form self. This process is known to be pivotal in preventing allergic & autoimmune diseases.

• Public health messages must start spreading the truth about the hyper-hygiene theory. Antibiotic chemicals & pesticides in daily household & general use are killing off normal microbes. Restriction of normal developmental exposure to natural environmental products, & exposing humans & their microbiota to toxins is probably behind far more disease that mild infection.

 

• Normal immune stimulation occurring by exposure & processing of variably noxious food, microbes & natural xenobiotics is healthy. This is disrupted by many man-made persistent chemicals. These & medicinal antibiotics are toxic to our commensal microbes, & our NRF2 metabolism, & should be avoided.

• Not attending to this truth feeds into the profits of highly advertised ‘sanitation’ products, including mouth washes. Sensible advice is to wash/wipe items with water or minimal mild environmentally friendly soaps/detergents until they look & small clean

 

• Weight gain in malnourished children given antibiotics may occur but if linear growth is not, the increased weight gain may be metabolic risky central fat.

• The only time very careful microbe killing should arise is where there are truly immunosuppressed persons or sites where surgery takes place ie hospitals.

b)“Over-fat & Under- muscled”; Humans are Fat From Birth (human specific) [Energy conservation]

• Muscle is a high metabolic rate tissue & generates work & heat whereas subcutaneous fat insulates body & efficiently stores, rather than uses, large amounts of energy.

• Metabolically safe lower body/peripheral subcutaneous fat depots develop - especially in pregnant/lactating women with 2 brains to buffer.

• Public health staff should understand & lead the community/primary health care professionals’ understanding of the different fat store morphology, health & health care implications

• This is probably an expensive tissue trade-off – “muscle for fat to conserve energy for the brain”.

• There are gender, age & ethnic group differences, eg buttock fat in some black groups, hip & thigh in white groups – mostly women.

• Treatment needs for the peripherally over weight are largely about locomotion, musculoskeletal, hygiene & body shape acceptance problems. Conversely the centrally overweight need urgent nutritional coaching & enablement to increase whole food intake for improved weight loss & metabolic health

• Human neonates are born fat – adipose tissue fat is a probable energy buffer for the brain which uses > 85% of the body’s energy at birth.

• These depots can be very large, & sometimes involves total body subcutaneous +/- central adipose (the classic Pickwick shape)

• Some individuals/groups having high subcutaneous fat reserves (gatherer phenotype), need low impact, upper body physical activity, (walking and carrying) whereas the slim-limbed, centrally obese (hunter phenotype) should work up to more intense, locomotor & upper body based activities, (hunter phenotype) which also tends to decrease visceral fat

 

• By storing fat safely away from high metabolic tissue (brain, liver, muscle, pancreas) the micronutrient to macronutrient ratio becomes larger & healthier.

  

Slow Growth and development [Energy Conservation]

• Human infants grow & develop slowly, possibly to allow adequate continuous supplies of energy to be channelled to the brain

• Slow growth allows time to accumulate fat reserves & in turn ensure the brain always has enough energy to develop. Note human breast milk is geared towards ‘brain nutrients’. NB partial weaning is earlier (4 rather than 6 months) in humans due to high energy demand of the infants brain

• Public health science needs to be geared to understand that humans grow & develop slowly, but have good powers of repair – & nutrition is behind this.

• A co-adaptation, to the ability to live long, is menopause, which prevents long lived women from breeding past 50y, possibly enhancing care of grandchildren.

• Slow growth & development has allowed the transmission of knowledge & culture

• Public health services need to increase aid to establish breast feeding in all women but particularly the obese with MetS, for whom this is more difficult. Large breasts & less healthy pregnancies & infants make this help all the more important – breast milk helps decrease the risk of the next generation being obese. Note - milk rarely ‘dries up’ unless suckling (or breast milk expressing) stops.

 

• Slow growth & delayed reproduction can only occur if there are very robust cell protection & maintenance mechanisms vis à vis the micronutrient dependant NRF2 cell protection system.

• Public health workers may need to promote total breast feeding of babies to 4-6 months then partial breast feeding for longer for 18 months+, ideally.

 

• Healthy longevity depends on a high ratio of micronutrient to macronutrients - degeneration sets in after youth when inherent reserve in cells declines

• Feeding children at (pre-) school is likely to be very cost effective. Improved nutrition whilst growing & developing is known to return children closer to their physical , metabolic & cognitive potential.

 

• When the micronutrient to macronutrient ratio is extremely low from preconception, central obesity & lean tissue deficiency rapidly associate with degenerative change; even pre-maturation. Although puberty is early with MetS & TIIDM , polycystic ovary syndrome & male gonadal hypo-function impair fertility. Teen pregnancies are decreasing in some groups with low socioeconomic status, poor nutrition & obesity. At the same time poverty is over represented in various ethnic groups, so falling fertility and not reaching their reproductive potential may be an ethnic survival problem.

• Public health should have policies that makes the most of the NRF2 potential for regeneration & repair - this means that it is worth feeding those with likely substandard nutrition eg prisoners, other wards of state, hospital & rest home residents healthy food – for social, developmental & ultimately economic reasons.

  

• Public health should ensure that the whole population is feed well from pre-conception to old age as it will save money by having a population at lower risk of physical, neurological & mental health dysfunction, & will keep people in work for longer.

  

• Public health study, action & advocacy on nutrition, from food production planning to the meal table, will help keep far more of the human race disease free, reproducing successfully & help ensure good quality survival.