Matoverfølsomhet – et paradigmeskifte

Artikkel skrevet i 2011 som nevner mange viktige poenger. Blandt annet at vagus svekkes ved IBS og at det gir andre plager, spesielt hudplager.

Click to access matoverfoelsomhet_aip_1_2011w_v2.pdf

Dessuten hadde mange pasienter ekstra-intesti- nale symptomer og skåret høyt på «Subjective Health Complaints» (1). Påfallende mange anga at de hadde kronisk tretthet samt leddsmerter med morgenstivhet uten påvisbar artritt. Livskvaliteten var til dels be- tydelig redusert (2).

Over 50% av pasientene tilfreds- stilte kravene til en psykiatrisk diag- nose. Men hvor mye av de psykologiske problemene kan være sekundære? Inntil for knapt 20 år siden ble også magesårsykdommen regnet som en psykosomatisk sykdom. De psykolo- giske problemene vi så hos ulcuspasi- entene var ganske like de vi nå finner hos de matoverfølsomme, og vi har enda friskt i minnet hvordan alle pro- blemene hos ulcuspasientene, in- kludert de psykologiske, «blåste bort» etter fjerning av magesårbakterien Helicobacter pylori (4).

Kun sykdomspesifikk angst eller for- ventninger om plager var signifikante uavhengige prediktorer. Disse pre- diktorene forklarte dog til sammen ikke mer enn 10% av variansen i mageplagene, og alder var eneste signifikante prediktor av ekstra- intestinale plager. Det vil si at 90% av variansen i grad av somatiske plager ikke kunne forklares av psyko- logiske faktorer. Vi tror derfor nå at mange av de psykologiske problemene ved matoverfølsomhet er sekundære og at betydningen av psykologiske faktorer som årsak til matoverfølsomhet kan være betydelig overdrevet.

Vi kunne vise at et tungt fordøyelig, men fermenter- bart karbohydrat, som laktulose, ofte reproduserte pasientens plager (6). tester på klassisk IgE-sensitivisering mot spesifikke kostproteiner, deri- mot, var sjeldent positive. Det virker som om mageplagene først og fremst trigges av tungt fordøyelige karbo- hydrater og ikke spesielt av proteiner i kosten. Dessuten, at plagene kunne reproduseres av mat, viser at pasien- ten har rett – plagene kan skyldes maten! Det passer med at pasientene ikke har plager om natta, når de faster, etter tarm- skylling eller når de får tømt seg fullstendig.

Over 60% av pasientene hadde indikasjon på atopisk sykdom (Dette er hud- og slimhinnerelaterte sykdommer som allergi, tørr hud, kløe, m.m.)

Histamin øker sympatisk og redusert para- sympatisk (vagal) tonus, som også er karakteristisk for pasienter med funksjonelle mageplager (16, 17). Slik endret autonom aktivitet kan være et resultat av IgE-mediert histaminfrigjøring fra lokalt sensibili- serte mastceller (18).

Systemiske symptomer som kro- nisk tretthet og leddsmerter hos pasi- enter med IBS har tidligere ofte blitt forklart som somatisering av psykolo- giske problemer, men det finnes andre muligheter. For eksempel er det nylig rapportert at symptomer ved kronisk tretthetssyndrom kan behandles med en B-celle-antagonist (rituximab) (21). I likhet med de matoverfølsomme, har pasienter med kronisk tretthets- syndrom ofte IBS og endret mikro- flora som kan være av betydning for immunaktiveringen hos disse pasi- entene (22). Hos matoverfølsomme med IBS har vi nylig påvist økt nivå av B-celle aktiverende faktor (BAFF) i blod og tarmskyllevæske (23). BAFF er relatert til autoimmunitet og lokal immunaktivering i tarmen («lokal allergi») (24).

At karbohydrater kan reprodusere mageplagene hos pasienter med IBS og matoverfølsomhet, er verdt å merke seg, og mye tyder på at dette allerede nå bør få terapeutiske konsekvenser (27). Vi ser med andre ord for oss et paradigmeskifte når det gjelder utredning og behandling av pasienter med IBS og matoverfølsomhet.

Central sensitisation in visceral pain disorders

Nevner hvordan IBS skaper sentralsensitering og hyperalgesia andre steder enn bare tarmen, og bidrar til mange muskel- og ledd problemer. Nevner at dette spesielt skjer i korsryggen hvor sensoriske nerver fra tarmen treffer samme nerve i ryggmargen som de sensoriske nervene fra beina.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1856337/

The concept of visceral hyperalgesia has been examined in a variety of functional gastrointestinal disorders (FGIDs), including oesophagitis, gastro‐oesophageal reflux disease, non‐ulcer dyspepsia, gastroparesis, and irritable bowel syndrome (IBS). Visceral hypersensitivity has also been demonstrated in non‐gastrointestinal disorders such as interstitial cystitis and ureteric colic.1 Although the pathophysiological mechanisms of pain and hypersensitivity in these disorders are still not well understood, exciting new developments in research have been made in the study of the brain‐gut interactions involved in the FGIDs.

In this issue of Gut, Sarkar and colleagues2 address the phenomenon of temporal summation of pain, termed “wind‐up”, and its relationship to central sensitisation and secondary visceral pain hyperalgesia caused by acidification of the oesophagus (see page 920). Also in this issue of Gut, Drewes and colleagues3 examine peripheral and central sensitisation using both mechanical and thermal stimuli in patients with oesophagitis compared with control subjects (see page 926). They found that in patients with oesophagitis, the interaction between central and peripheral nociceptive input may help explain patient symptoms. Understanding the implications of these two studies requires examining the concept of central sensitisation in visceral pain disorders. Both of these studies have important clinical and research ramifications for the study of FGIDs.

“Hypersensitivity in IBS patients is not just limited to the gut and more widespread alterations in central pain processing may be involved in this chronic pain disorder”

The most pronounced hyperalgesia appears to occur at the lumbosacral level at which colon and lower extremity nociceptive afferents are likely to converge onto common spinal segments, explaining why patients had higher thermal hypersensitivity in the foot than in the hand (see fig 11).14,15,19

Non-Celiac Gluten Sensitivity: The New Frontier of Gluten Related Disorders

Nyeste oppdateringen på gluten, som nevner at det ikke er glutenet i korn som er det største problemet, men FODMAPs. Ikke-cøliakisk glutenintoleranse er reell for noen, men ikke så mange som vi trodde. FODMAPs gjelder flere. Nevner også at dette kan gjelde opptil 30% av befolkningen. Beskriver symptomer på glutenintoleranse, og at pasienten ofte har oppdaget et fobindelse selv med sine symptomer når de kutter gluten-korn.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3820047/

Non Celiac Gluten sensitivity (NCGS) was originally described in the 1980s and recently a “re-discovered” disorder characterized by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing food, in subjects that are not affected with either celiac disease (CD) or wheat allergy (WA). Although NCGS frequency is still unclear, epidemiological data have been generated that can help establishing the magnitude of the problem. Clinical studies further defined the identity of NCGS and its implications in human disease. An overlap between the irritable bowel syndrome (IBS) and NCGS has been detected, requiring even more stringent diagnostic criteria. Several studies suggested a relationship between NCGS and neuropsychiatric disorders, particularly autism and schizophrenia. The first case reports of NCGS in children have been described. Lack of biomarkers is still a major limitation of clinical studies, making it difficult to differentiate NCGS from other gluten related disorders. Recent studies raised the possibility that, beside gluten, wheat amylase-trypsin inhibitors and low-fermentable, poorly-absorbed, short-chain carbohydrates can contribute to symptoms (at least those related to IBS) experienced by NCGS patients. In this paper we report the major advances and current trends on NCGS.

In order to develop a consensus on new nomenclature and classification of gluten-related disorders, a panel of experts first met in London, in February 2011. The panel proposed a series of definitions and developed a diagnostic algorithm that has been recently published [4].

After the 2011 London Meeting, many new papers have been published on GS. Although its frequency in the general population is still unclear, epidemiological data have been generated that can help establish the magnitude of the problem. Clinical studies further defined the identity of GS and its possible implications in human disease. An overlap between the irritable bowel syndrome (IBS) and GS has been suspected, requiring even more stringent diagnostic criteria. The first case reports of GS in children have been described. Lack of biomarkers is still a major limitation of clinical studies, making the differential diagnosis with other gluten related disorders, as well conditions independent to gluten exposure, difficult.

Evaluation and discussion of this new information was the aim of a Second Expert Meeting on GS that was held in Munich, November 30–December 2, 2012. In this paper we report the major advances and current trends on GS, as presented and debated at the Munich meeting.

According to recent population-based surveys performed in Northern Europe, the prevalence of IBS in the general adult population is 16%–25% [11,12]. In a selected (and, therefore, probably biased) series of adults with IBS, the frequency of NCGS, documented by a double-blind, placebo-controlled challenge, was 28% [13]. In the large study performed by Carroccio et al., 276 out of 920 (30%) subjects with IBS-like symptoms, according to the Rome II criteria, suffered from wheat sensitivity or multiple food hypersensitivity, including wheat sensitivity [14]. Should a consistent proportion of IBS patients be affected with NCGS, the prevalence of NCGS in the general population could well be higher than CD (1%).

NCGS is characterized by symptoms that usually occur soon after gluten ingestion, disappear with gluten withdrawal and relapse following gluten challenge, within hours or few days. The “classical” presentation of NCGS is a combination of IBS-like symptoms, including abdominal pain, bloating, bowel habit abnormalities (either diarrhea or constipation), and systemic manifestations such as “foggy mind”, headache, fatigue, joint and muscle pain, leg or arm numbness, dermatitis (eczema or skin rash), depression, and anemia [2,15]. When seen at the specialty clinic, many NCGS patients already report the causal relationship between the ingestion of gluten-containing food and worsening of symptoms. In children, NCGS manifests with typical gastrointestinal symptoms, such as abdominal pain and chronic diarrhea, while the extra-intestinal manifestations seem to be less frequent, the most common extra-intestinal symptom being tiredness [16].

In a second study, Biesiekirski et al. reported on 37 patients with IBS/self-reported NCGS investigated by a double-blind crossover trial. Patients were randomly assigned to a period of reduced low-fermentable, poorly-absorbed, short-chain carbohydrates (fermentable oligo-, di-, and mono-saccharides and polyols = FODMAPs) diet and then placed on either a gluten or whey proteins challenge. In all participants, gastrointestinal complaints consistently improved during reduced FODMAP intake, but significantly worsened to a similar degree when their diets included gluten or whey proteins [21].FODMAPS list includes fructans, galactans, fructose, and polyols that are contained in several foodstuffs, including wheat, vegetables, and milk derivatives. These results raise the possibility that the positive effect of the GFD in patients with IBS is an unspecific consequence of reducing FODMAPs intake, given that wheat is one of the possible sources of FODMAPs.

The pathophysiology of NCGS is under scrutiny. In the study conducted by Sapone et al. [2], NCGS subjects showed a normal intestinal permeability and claudin-1 and ZO-1 expression compared with celiac patients, and a significantly higher expression of claudin-4.

King Corn dokumentar

En av de første kommentarene i denne dokumentaren setter standarden:

«We recently learned that people who grew up the way we did are basicly made up of corn.

…what the heck!!!»

La oss gi dette litt tid synke inn. Du blir hva du spiser. I de aller fleste varene i butikken er korn/mel en viktig ingrediens. I tillegg anbefaler myndighetene oss at 3 av 4 måltider skal bestå av korn. Men ikke nok med det. Kyrne blir foret med korn også, hele 60% av deres diett består av korn. Det er så mye at om de må slaktes før de dør av acidose (lav pH i blod). Årsaken til at kyrne fores på så mye korn er at det øker deres vekt raskest, slik at de raskest mulig kan slaktes og komme ut på markedet. Om kyrne skulle fores på naturlig gress ville de brukt mer enn ekstra år før de ble store nok til å slaktes.

Denne dokumentaren er smekk full av viktige avsløringer som alle bør vite om.

Spectrum of gluten-related disorders: consensus on new nomenclature and classification

Oppdatert forhold til ikke-cøliakisk glutenintoleranse fra 14 eksperter i USA.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3292448/

This review will summarize our current knowledge about the three main forms of gluten reactions: allergic (wheat allergy), autoimmune (celiac disease, dermatitis herpetiformis and gluten ataxia) and possibly immune-mediated (gluten sensitivity), and also outline pathogenic, clinical and epidemiological differences and propose new nomenclature and classifications.

It is now becoming apparent that reactions to gluten are not limited to CD, rather we now appreciate the existence of a spectrum of gluten-related disorders. The high frequency and wide range of adverse reactions to gluten raise the question as to why this dietary protein is toxic for so many individuals in the world. One possible explanation is that the selection of wheat varieties with higher gluten content has been a continuous process during the last 10,000 years, with changes dictated more by technological rather than nutritional reasons.

Additionally, gluten is one of the most abundant and diffusely spread dietary components for most populations, particularly those of European origin. In Europe, the mean consumption of gluten is 10 g to 20 g per day, with segments of the general population consuming as much as 50 g of daily gluten or more [6667] All individuals, even those with a low degree of risk, are therefore susceptible to some form of gluten reaction during their life span.

Does gluten sensitivity in the absence of coeliac disease exist?

Artikkel som nevner den fremadstormende forskningen som gjøre på ikke-cøliakisk glutensensitivitet.

http://www.bmj.com/content/345/bmj.e7907

However, the number of patients consuming a gluten-free diet seems greatly out of proportion to the projected number of patients with coeliac disease. Marketers have estimated that 15-25% of North American consumers want gluten-free foods,4 5

A third of patients (n=276) showed clinical and statistically significant sensitivity to wheat and not placebo, with worsening abdominal pain, bloating, and stool consistency. The evidence therefore suggests that, even in the absence of coeliac disease, gluten based products can induce abdominal symptoms which may present as irritable bowel syndrome.

For patients who report wheat intolerance or gluten sensitivity, exclude coeliac disease (with endomysial and/or tissue transglutaminase antibodies and duodenal biopsies on a gluten containing diet) and wheat allergy (IgE serum assay or skin prick test to wheat). Those patients with negative results should be diagnosed with non-coeliac gluten sensitivity. These patients benefit symptomatically from a gluten-free diet. They should be told that non-coeliac gluten sensitivity is a newly recognised clinical entity for which we do not yet fully understand the natural course or pathophysiology.

The gluten syndrome: A neurological disease

Nevner det meste om gluten relatert til nerveproblemer. Noe av årsaken ligger i at det blir en autoimmun plage med antistoffer i nerver, som etter hvert gir nerveskader. 64% av de med cøliaki har også nevropati.

http://integrativehealthconnection.com/wp-content/uploads/2011/11/The-gluten-syndrome-A-neurological-disease-21.pdf

Hypothesis: Gluten causes symptoms, in both celiac disease and non-celiac gluten-sensitivity, by its adverse actions on the nervous system.
Many celiac patients experience neurological symptoms, frequently associated with malfunction of the autonomic nervous system. These neurological symptoms can present in celiac patients who are well nourished. The crucial point, however, is that gluten-sensitivity can also be associated with neurological symptoms in patients who do not have any mucosal gut damage (that is, without celiac disease).
Gluten can cause neurological harm through a combination of cross reacting antibodies, immune com- plex disease and direct toxicity. These nervous system affects include: dysregulation of the autonomic nervous system, cerebella ataxia, hypotonia, developmental delay, learning disorders, depression, migraine, and headache.
If gluten is the putative harmful agent, then there is no requirement to invoke gut damage and nutri- tional deficiency to explain the myriad of the symptoms experienced by sufferers of celiac disease and gluten-sensitivity. This is called ‘‘The Gluten Syndrome”.

A mechanism for such nerve damage might be through autoimmune damage [15]. A number of nerve and brain antibodies have been detected. Anti-ganglioside antibodies have been detected in 64% of patients with celiac disease who had also been troubled with some sort of neuropathy [16]. These auto-antibodies have been shown to bind to a number of critical nerve sites that will go on to damage the nerve.

Gluten-free diet reduces adiposity, inflammation and insulin resistance associated with the induction of PPAR-alpha and PPAR-gamma expression.

Nevner at gluten-fri er viktig å teste ut i behandling av overvekt og metabolske sykdommer, siden det reduserer betennelser.

http://www.ncbi.nlm.nih.gov/m/pubmed/23253599

«There was an improvement in glucose homeostasis and pro-inflammatory profile-related overexpression of PPAR-γ.»

«Our data support the beneficial effects of gluten-free diets in reducing adiposity gain, inflammation and insulin resistance. The data suggests that diet gluten exclusion should be tested as a new dietary approach to prevent the development of obesity and metabolic disorders.»

Lifestyle and nutritional imbalances associated with Western diseases: causes and consequences of chronic systemic low-grade inflammation in an evolutionary context

Nevner hvordan betennelsesmarkører og insulinsensitivitet henger sammen. Svært mange viktige poenger og en god oversiktig i denne studien. Info om betennelser, insulin, tyroksin, fett, oksidativt stress, D-vitamin, m.m.

http://www.jnutbio.com/article/S0955-2863(13)00054-5/abstract

http://www.jnutbio.com/article/S0955-2863(13)00054-5/fulltext 

Fra evolusjonens side er insulinresistens en overlevelsesmekanisme. Hjernen og nervesystemet bruker 20% av energien glukose metabolismen gir oss og for overlevelse er hjernen førsteprioritet. Når det er betennelser i kroppen vil immunforsvaret naturlig bruke opp mye av glukosen i blodet slik at det går på bekostning av hjernens energitilgang. Da må hjernen sette igang en «insulinresistens» for å sørge for at insuline ikke fjerner glukosen i blodet. Insulinresistens er en livsviktig mekanisme som skal fungere i kort tid av gangen (noen dager). Om det blir en kronisk systemisk betennelse blir det store problemer i kroppen som etter mange år gir utslag i livsstilsykdommer.

«Our sensitivity to develop insulin resistance traces back to our rapid brain growth in the past 2.5 million years. An inflammatory reaction jeopardizes the high glucose needs of our brain, causing various adaptations, including insulin resistance, functional reallocation of energy-rich nutrients and changing serum lipoprotein composition. «

Betenneler er en naturlig helbredelsesreaksjon ved skade eller infeksjoner. Men i vår vestlige kultur har vi introdusert en rekke «falske» betennelsestriggere. Altså elementer som gir kroppen betennelser uten at det foreligger en skade. Når betennelser blir kroniske er det ett eller annen «kronisk» vi gjør i vår livsstil som opprettholder betennelsene. Maten vi spiser er den viktigste bidragsyteren spesielt siden vårt moderne kosthold inneholder så mange betennelsestriggere. Bl.a. sukker og mel og overvekt av raffinerte næringsfattige karbohydrater. Skal man bli frisk fra kroniske plager og betennelser i muskel- og skjelettapparatet må man fjerne de falske betennelsestriggerene fra hverdagen.

«With the advent of the agricultural and industrial revolutions, we have introduced numerous false inflammatory triggers in our lifestyle, driving us to a state of chronic systemic low grade inflammation that eventually leads to typically Western diseases via an evolutionary conserved interaction between our immune system and metabolism. The underlying triggers are an abnormal dietary composition and microbial flora, insufficient physical activity and sleep, chronic stress and environmental pollution. «

Betenneler blir viktigere og viktigere i helsesammenheng. Hjerte/kar problemer, flere kreftformer, degenererende sykdommer, m.m. har alle samme utgangspunkt: systemisk betennelse og medfølgende insulinresistens.

«In recent years, it has become clear that chronic systemic low grade inflammation is at the basis of many, if not all, typically Western diseases centered on the metabolic syndrome. The latter is the combination of an excessive body weight, impaired glucose homeostasis, hypertension and atherogenic dyslipidemia (the “deadly quartet”), that constitutes a risk for diabetes mellitus type 2, cardiovascular disease (CVD), certain cancers (breast, colorectal, pancreas), neurodegenerative diseases (e.g., Alzheimer’s disease), pregnancy complications (gestational diabetes, preeclampsia), fertility problems (polycystic ovarian syndrome) and other diseases [1]. Systemic inflammation causes insulin resistance and a compensatory hyperinsulinemia that strives to keep glucose homeostasis in balance. Our glucose homeostasis ranks high in the hierarchy of energy equilibrium, but becomes ultimately compromised under continuous inflammatory conditions via glucotoxicity, lipotoxicity, or both, leading to the development of beta-cell dysfunction and eventually Type 2 diabetes mellitus [2]

Det er en evolusjonært tilpasset sammenheng mellom kroppsvekt og metabolisme hos dyr. Jo større dyret er jo mer energi krever metabolismen. Hjernen og nervesystemet er et av de mest energikrevende organene så når mennesket etterhvert utviklet en enorm hjerne relativt til kroppsvekt måtte dette gå på bekostning av andre energikrevende organer. Hos oss har tarmene blitt mindre.

«Our brain consumes 20–25%2 of our basal metabolism [11][12][13][14][15][16][17] and [20] and is thereby together with the liver (19%2), our gastrointestinal tract (15%2), and skeletal musculature (15%2) among the quantitatively most important organs in energy consumption [19]

«There is a linear relationship between body weight and basal metabolism among terrestrial mammals (Fig. 2). This apparently dogmatic relationship predicts that, due to the growth of our brain, other organs with high energy consumption had to be reduced in size, what in evolution is known as a “trade-off”.3 As a consequence of this “expensive tissue hypothesis” of Aiello and Wheeler [19], our intestines, amongst others, had to become reduced in size. «

Når vi får mange på glukose i blod blir det konkurranse mellom organene om å få nok. Dette skjer bl.a. under faste, i graviditet og under infeksjoner og betennelser. Hjernen vil alltid være førsteprioritet. Derfor har evolusjonen utviklet insulinresistens for å sørge for at glukose alltid er tilgjengelig for hjernen, uansett hvor mye andre organer eller immunforsvar prøver å ta det.

«A glucose deficit leads to competition between organs for the available glucose. As previously mentioned, this occurs during fasting, but also during pregnancy and infection/inflammation. «
«During competition between organs for glucose, we fulfill the high glucose needs of the brain by a reallocation of the energy-rich nutrients, and to that end, we need to become insulin resistant.»

Insulinresistens påvirker også blodgjennomstrømning ved at det hemmer vasodilatsjon (utvidelse av blodkar). Når blodårene blir trangere må hjertet pumpe hardere og vi får høyt blodtrykk. I tillegg vil manglende fleksibilitet i blodårene gjøre at nyrene blir veldig sensitive for salt. Nyrene kan hjelpe i kontrollen av blodtrykk ved å senke eller øke saltmengden, men dette er en sekundær funksjon. Det er blodkarenes utvidelse og sammentrekning som er er førsteprioritet i blodtrykkskontroll. Når denne funksjonen blir dårlig må nyrene jobbe på høygir og blir etter hvert overarbeidet og skadet.

» For example, the concomitant hypertension has been explained by a disbalance between the effects of insulin on renal sodium reabsorption and NO-mediated vasodilatation, in which the latter effect, but not the first, becomes compromised by insulin resistance, causing salt sensitivity and hypertension [54]

Her er en gjennomgang av alle aspektene og mekanismene i kroppen som påvirkes av lav-grads betennelser og medfølgende insulinresistens.

«However, it becomes increasingly clear that we could better refer to it as the “chronic systemic low-grade inflammation induced energy reallocation syndrome”. The reason for this broader name derives from the recognition that insulin resistance is only part of the many simultaneously occurring adaptations. To their currently known extent, these adaptations and consequences are composed of:
(i) reduced insulin sensitivity (glucose and lipid redistribution, hypertension),
(ii) increased sympathetic nervous system activity (stimulation of lipolysis, gluconeogenesis and glycogenolysis),
(iii) increased activity of the HPA-axis [hypothalamus-pituitary-adrenal gland (stress) axis, mild cortisol increase, gluconeogenesis, with cortisol resistance in the immune system],
(iv) decreased activity of the HPG-axis (hypothalamus-pituitary-gonadal gland axis; decreased androgens for gluconeogenesis from muscle proteins, sarcopenia, androgen/estrogen disbalance, inhibition of sexual activity and reproduction),
(v) IGF-1 resistance (insulin-like growth factor-1; no investment in growth) and vi) the occurrence of “sickness behavior” (energy-saving, sleep, anorexia, minimal activity of muscles, brain, and gut) [3]

Mennesket er det dyret med størst hjerne. Og siden hjernen er stappet full av nervetråder som krever svært mye energi for å fungere blir menneskekroppen svært sensitiv for glukose. Hvis vi får lite glukosetilgang har kroppen en etablert en robuste tilpasningsmekanismer for å overleve, men dette gjelder kun i kortere perioder.

«Summarizing thus far, we humans are extremely sensitive to glucose deficits, because our large brain functions mainly on glucose. During starvation, pregnancy and infection/inflammation, we become insulin resistant, along with many other adaptations. «

De forskjellige tilpasningsmekanismene vi har for å overleve ved betennelsestilstander (inkl insulinresisten) viser oss hvor tett immunsystemet og metabolismen er koblet i kroppen vår.  Det er ikke to forskjellige systemer, men vevet inn i hverandre.

«The metabolic adaptations caused by inflammation illustrate the intimate relationship between our immune system and metabolism. This relation is designed for the short term. In a chronic state it eventually causes the metabolic syndrome and its sequelae. We are ourselves the cause of the chronicity. Our current Western lifestyle contains many false inflammatory triggers and is also characterized by a lack of inflammation suppressing factors. These will be described in more detail below.»

Denne studien nevnte tidligere at betennelser skaper insulinresisten som følge av en naturlig overlevelsesmekanisme ved skader og akutte sykdommer. Men i vår moderne hverdag har vi en lang rekke «falske betennelsesfaktorer» som gir oss betennelser uten at det foreligger skade. Her er en oversikt over de viktigste «falske betennelsefaktorer» vi må se opp for om vi ønsker å bli kvitt smerter og livsstilssykdommer:

«Among the pro-inflammatory factors in our current diet, we find:
– the consumption of saturated fatty acids [82] and industrially produced trans fatty acids [83] and [84], a high ω6/ω3 fatty acid ratio [85], [86] and [87],
– a low intake of long-chain polyunsaturated fatty acids (LCP) of the ω3 series (LCPω3) from fish [88] and [89],
– a low status of vitamin D [90], [91] and [92], vitamin K [93] and magnesium[94], [95] and [96],
– the “endotoxemia” of a high-fat low-fiber diet [97] and [98],
– the consumption of carbohydrates with a high glycemic index and a diet with a high glycemic load [99] and [100],
– a disbalance between the many micronutrients that make up our antioxidant/pro-oxidant network [101], [102] and [103], and
– a low intake of fruit and vegetables [103] and [104].
The “dietary inflammation index” of the University of North Carolina is composed of 42 anti- and proinflammatory food products and nutrients. In this index, a magnesium deficit scores high in the list of pro-inflammatory stimuli [105]. Magnesium has many functions, some of them, not surprisingly, related to our energy metabolism and immune system, e.g., it is the cation most intimately connected to ATP [95].
Indirect diet-related factors are
– an abnormal composition of the bacterial flora in the mouth [106], gut [106] and [107], and gingivae [108], [109] and [110].
– Chronic stress[111] and [112],
– (passive) smoking and
– environmental pollution [77],
– insufficient physical activity [113],[114], [115], [116], [117] and [118] and
– insufficient sleep [119], [120], [121], [122] and [123] are also involved.»

«Diets high in refined starches, sugar, saturated and trans fats, and low in LCPω3, natural antioxidants, and fiber from fruits and vegetables, have been shown to promote inflammation [82], [83], [84], [129],[130] and [131] (Table 1).»

«Molecular oxygen is essential to aerobic life and, at the same time, an oxidizing agent, meaning that it can gain electrons from various sources that thereby become “oxidized,” while oxygen itself becomes “reduced”[252] and [253]. In general terms, an antioxidant is “anything that can prevent or inhibit oxidation” and these are therefore needed in all biological systems exposed to oxygen [252]
«The emergence of oxygenic photosynthesis and subsequent changes in atmospheric environment [254] forced organisms to develop protective mechanisms against oxygen’s toxic effects [255]. »

» Damage by oxidation of lipids[262], [265] and [266], nucleic acids and proteins changes the structure and function of key cellular constituents resulting in the activation of the NFκB pathway, promoting inflammation, mutation, cell damage and even death [252], [260] and [267] and is thereby believed to underlie the deleterious changes in aging and age-related diseases [102] and [244]

»
Fig. 8. Antioxidant defense mechanisms. An overview of the antioxidant system present in the human body. Various types of antioxidant systems have developed through time, reflecting different selection pressures. Different forms have developed for the same purpose, for example, SODs, peroxidases and GPx are important members of the antioxidant enzyme capacity group. Tocopherols and ascorbic acid, as representatives of the antioxidant network, are manufactured only in plants, but are needed by animals. Ascorbic acid is an essential antioxidant, but cannot be synthesized by Homo sapiens. In humans, therefore, antioxidant defense against toxic oxygen intermediates comprises an intricate network which is heavily influenced by nutrition. GR, glutathione reductase; GSG, reduced glutathione; GSH-Px, glutathione peroxidase; GSSG, oxidized glutathione; GST, glutathione-S-transferase; MSR, methionine sulphoxide reductase; PUFA, polyunsaturated fatty acids; S-AA, sulphur amino-acids; SH-proteins, sulphydryl proteins; SOD, superoxide dismutase; Fe Cu, transition metal-catalysed oxidant damage to biomolecules.»

«A certain level of ROS may also be essential to trigger antioxidant responses [276]

«Chronic inflammation results in the chronic generation of free radicals, which may cause collateral damage and stimulate signaling and transcription factors associated with chronic diseases [294] and [295]

«Our diet is composed of millions of substances that are part of a biological network. In fact, we eat “biological systems” like a banana, a fish or a piece of meat. There is a connection between the various nutrients in these systems. In other words, there is a balance and an interaction that is part of a living organism. »

«As clearly explained by Rose[328]: «If everyone smoked 20 cigarettes a day, then clinical, case–control and cohort studies alike would lead us to conclude that lung cancer was a genetic disease; and in one sense that would be true, since if everyone is exposed to the necessary agent, then the distribution of cases is wholly determined by individual susceptibility”. In other words: “disease susceptibility genes” is a misnomer from an evolutionary point of view.»

«Hemminki et al.[326] stated that “if the Western population was to live in the same conditions as the populations of developing countries, the risk of cancer would decrease by 90%, provided that viral infections and mycotoxin exposures could be avoided”.»

«It has become clear that most, if not all, typically Western chronic illnesses find their primary cause in an unhealthy lifestyle and that systemic low grade inflammation is a common denominator.»