Feeding tube

Human Nutrition

Learning from patient safety incidents
The oral route is generally the most convenient and costs the least. A glycomacropeptide based protein substitute helps promote stable blood phenylalanine and branched chain amino acids in patients with phenylketonuria Posters from GMDI Nutritional management of an adult with Phenylketonuria with the use of a Glycomacropeptide-based PKU formula See all. Journal of medical radiation sciences. The GJ-tube is used widely in individuals with severe gastric motility, high risk of aspiration, or an inability to feed into the stomach. Submit Manuscript Journal Impact Factor 1. Only after that can you start the postabsorptive phase, Marked by using glycogen as your source of blood sugar.

B. Nutritional assessment

Covidien Kangaroo ePump Enteral Feeding Pump Device

Also, this method is rarely used in humans, so it may not be easy to make any practical use of. In any case, none of this would suggest that eating plant fibre will help colitis in any way, given that the issue appears to depend on inability to use the butyrate.

There is not clear evidence that fibre intake helps with IBD, and in fact, "low residue" or "low fibre" diets are usually recommended see below.

In case you were wondering, "residue" means anything that survives digestion, and comes all the way through the intestines. That includes fibre , but also microorganisms, and secretions and cells shed from the alimentary tract.

While there are studies that support the benefit of fibre in IBD, there are others showing harm. The evidence is mixed enough to be called weak and inconclusive [Kap]. Anecdotes such as the " Crohn's Carnivore " suggest a different solution might hold for some:. That experience runs both with and possibly against current dietary guidelines for IBD.

In a review [Bro] , the authors show that most guidelines advise low fibre intake, especially during flares. Some also advise low fat intake, and in particular, to eat lean meat. I'm not sure whether the Crohn's Carnivore was eating lean or fatty meat during his year of healing. At first blush, the low fat advisory looks like just another "extra-mile" kind of recommendation, in which guideline writers are throwing in other ideas about healthy diet for good measure.

However, they state that it comes from the reported reactions of some patients. One wonders if there are conflations. Later, the authors specifically say that there is little to support or refute a low fat recommendation. Another anecdote, this time elevated to "case study" level, because physicians penned it, comes from the Evolutionary Medicine Working Group, in Budapest, Hungary [Tot].

They report complete resolution of symptoms in a child with Crohn's and cessation of medications from an essentially meat-only diet. The exception was that patient was allowed some honey, but it was low enough that ketosis was maintained. This was a 2: The child had previously tried low fat, low fibre, and several medications without improvement.

It is interesting to note that even one dose of "paleo approved" fibre caused a flare up. In other words, a fibre-free ketogenic diet appears help IBD more than a diet including fibre, even a ketogenic diet including fibre. The idea that butyrate might be protective of colon cancer seems to have started in the s see, e.

This area of research is extensive, and I am by no means an expert. If you haven't guessed, that butyrate has a protective effect on colon cancer is the one statement I think is entirely defensible. For example butyrate's histone deacelytase HDAC inhibition is considered an important mechanism [Hin] , [Blo]. Gpra receptor activation is a recently identified mechanism [Sin]. In fact, the argument behind the relevance of the Gpra discovery is just as strong an argument for a ketogenic diet as for eating fibre!

This sentence is incorrect. That is, the researchers demonstrated that butyrate could substitute for niacin in activating these receptors, and that just as niacin activation of Gpra in fat cells is protective of cardiovascular disease, it may also be in diseases of the colon, and this argues for eating fibre to substitute for pharmalogic doses of niacin.

From a press release:. Their search for other activators identified butyrate, which led Ganapathy to find that not only is the Gpra receptor expressed on the surface of colon cells, but that with sufficient fiber intake, butyrate levels in the colon can activate it.

A critic pointed out that the cell receptors for SCFAs are facing the lumen, and therefore argued that beta-hydroxybutyrate from the portal side would be irrelevant. Indeed, the researchers using niacin also assume that the extremely high dose of niacin does not act sytemically, but rather reaches the lumen because of the super-high doses. So the statement I made above, about the argument for beta-hydroxybutyrate being equal to that for niacin is not correct.

The argument still stands that the beta-hydroxybutyrate metabolites activating targets inside could be where the majority of the benefits of butyate come from.

That is where the HDAC inhibition occurs and where the immune cell receptors are. At least one research group agrees with my speculation that the interior metabolites may be important for the effect [Siv]. SCFAs are low-affinity agonists for these receptors, and the normal luminal concentrations of these bacterial metabolites are in the millimolar levels, sufficient to activate these receptors from the luminal side.

However, some of the molecular targets for these metabolites are either inside the cells e. Therefore, concentrations of these metabolites inside the colonic epithelial cells and in the lamina propria are relevant to impact these molecular targets. The intracellular target HDAC is inhibited by butyrate and propionate at low micromolar concentrations. There are effective transport systems for SCFAs in the apical membrane of colonic epithelial cells e.

Even though the luminal concentrations of SCFAs are in the millimolar range, it is unlikely that they reach lamina propria at significant levels to activate the cell-surface receptors present on the mucosal immune cells. These metabolites are present only at micromolar levels in the portal blood [57], indicating that they undergo robust metabolism inside the colonic epithelial cells. This raises the question as to the physiological relevance of these bacterial metabolites to the activation of the cell-surface SCFA receptors in immune cells located in the lamina propria.

This ketone body is released from the cells into portal blood. Interestingly, as in the case of colitis, colorectal cancer appears to involve a dysfunction in ability to use butyrate.

Specifically, there are detrimental changes in membrane transport that reduce its entry into the cell [Gon]. Therefore, it's unclear that once the disease process has begun, increased fibre intake will be of any use.

Beta-hydroxybutyrate in the bloodstream, however, might. There is at least some preliminary evidence that butyrate in the bloodstream has similar effects on intestinal tissue as butyrate coming from the colon itself [Kor] , [Rol] , [Bar] , as does infusion of glutamine and acetoacetate, another ketone body [Rom].

Ketogenic diets do increase blood acetoacetate. These common mechanisms suggest that much or even all of the benefits obtainable by butyrate are equally achievable simply through ketogenic diets, making additional butyrate in the context of a ketogenic diet potentially superfluous. Even though it seems likely that a fibre-free ketogenic diet is not only sufficient for colon health, but better for treating colon disease, we might feel cautious about going without the butyrate from fibre, given the dire pronouncements from nutritional scientists.

Is there any other way to get butyrate? The most significant food source, butter, doesn't give much. That would take about a pound of butter! Stepping back, it should be obvious that carnivores such as felines and canines provide an important source of data relevant to this question. Carnivores have colons, and they are not normally in ketosis unless food is scarce. Either their colons don't need butyrate, or they are getting sufficient butyrate from some other source.

As it happens, there are microbes that ferment amino acids in to short chain fatty acids SCFAs , including butyrate.

Carnivores are known to get "animal fibre" from their prey. That is, amino acids from incompletely digested animal parts reach their colons and are fermented. In particular, in cheetahs, casein, collagen, and glucosamine have been shown to result in butyrate production comparable to fructo-oligosaccharides [Dep]. Beyond poorly digested animal sourced fibre, many amino acids are fermented into SCFAs, including butyrate [Ras] , and these amino acids are abundant in human intestines and colons and are fermented there [Vit] , [Dai] , [Nei] , [Wie].

I was unable to determine how much butyrate this would account for. I did find research comparing the SCFA levels produced in dogs under conditions of high fibre vs. This idea is supported by these observations:.

Colonocyte butyrate metabolism was investigated in experimental colitis in mice. Colonocytes isolated from colitic and normal control mice were incubated with [ 14 C]butyrate or glucose, and production of 14 CO 2 , as well as of intermediate metabolites acetoacetate, beta-hydroxybutyrate and lactate , was measured.

The effect of different substrate concentrations on oxidation was also examined. Production of beta-hydroxybutyrate was decreased and production of lactate increased in DSS colitis compared with controls. Increasing butyrate concentration from 10 to 80 mM enhanced oxidation in DSS colitis 0.

Surface and crypt epithelial cells showed similar ratios of butyrate to glucose oxidation. When 1 mM DSS was added to normal colonocytes in vitro, it did not alter butyrate oxidation.

The initial histological lesion of DSS administration was very patchy and involved crypt cells. Abnormal butyrate oxidation became apparent only after six days of DSS administration, at which time histological abnormalities were more widespread. Histological abnormalities preceded measurable defects in butyrate oxidation.

It was logical to assume that liver and muscle glycogen could serve as the fermentable substrate for lactate production in the stomach, but most of this should have been digested and absorbed by the small intes tine. Another possible source of ferment able substance which could survive passage through the small intestine is the protein- polysaccharides of the connective tissue ground substance found in abundance in the meat by-products and whole ground chicken.

The ground substance is made up of chondroitin sulfates and hyaluronic acid. The polysaccharide portion of these substances is composed of long chains of disaccharide units consisting of glucosa- mine or galactosamine and glucuronic acid.

The linkages of these polysaccharides are not such that they can be cleaved by the endogenous digestive enzymes found in the gut but they could be split by microbial enzymes.

However, the ability and timing of SCFA to augment adaptation in the neonatal intestine is unknown. Furthermore, the specific SCFA inducing the intestinotrophic effects and underlying regulatory mechanism s are unclear. Within each group, piglets were further randomized to examine acute 4, 12, or 24 hours and chronic 3 or 7 days adaptations. Indices of intestinal adaptation, including crypt-villus architecture, proliferation and apoptosis, and concentration of the intestinotrophic peptide, glucagon-like pepide-2 GLP-2 , were measured.

Indicative of an antiapoptotic profile, jejunal Bax: The intestinotrophic mechanism s underlying butyrate's effects may involve GLP Ultimately, butyrate administration may enable an infant with short-bowel syndrome to successfully transition to enteral feedings by maximizing their absorptive area. The question of whether or not to use probiotics continues to be debated. It may be important to communicate to IBD patients that high-fiber foods are not recommended, especially for those with CD, during flares or in the presence of active disease states, fistulas or strictures.

There appears to be a tendency among the dietary guidelines to restrict foods such as raw fruits, raw vegetables, beans, bran, popcorn, seeds, nuts, corn hulls, whole grains, brown rice and wild rice.

Although not mentioned, raw salads would also fall into this category. Few research studies are available to support or refute such a recommendation.

The topic needs further investigation because patients with malabsorption may be at risk of not obtaining their necessary essential fatty acids. Perhaps saturated fats should be limited, with more of an emphasis on more healthy fat intakes. The abundance of the AA-fermenting bacteria in the large intestine is very high and their number can reach up to per gram dry feces Smith and Macfarlane, Using the traditional plate counting technique, the authors have also reported that the dominant bacterial species for the utilization of single AA or pairs of AA are very different.

For instance, Clostridium bifermentans is the predominant bacteria for the utilization of lysine or proline, and pairs of AA e. Many species of bacteria utilize the same AA as substrates for growth Smith and Macfarlane, Overall, bacteria belonging to the Clostridium spp. The FOS and collagen showed comparable acetate production. Collagen not only had a high production of total SCFA but also resulted in a greater acetate to propionate ratio relative to all other substrates 8.

Considerable variation in BCFA ratios was observed among substrates. So, knowledge on the mechanisms involved in its membrane transport is relevant to both its physiological and pharmacological benefits.

Also, changes in transporter expression or function will have an obvious impact on the effect of BT, and therefore, knowledge on the regulation of its membrane transport seems particularly important. More specifically, BT is transported into normal colonic epithelial cells by both MCT1 and SMCT1, but its intracellular concentration is kept low because it is efficiently metabolized and effluxed from these cells by BCRP-mediated transport.

In these cells, BT accumulates intracellularly because it is inefficiently metabolized due to the fact that glucose becomes the primary energy source of these cells and because there is a reduction in BCRP expression.

Butyrate is thought to exert its cellular effects through the induction of histone hyperacetylation. We sought to determine the effects of a variety of the SCFA on colon carcinoma cell growth, differentiation and apoptosis. HT or HCT wild-type and pdeleted cells were treated with physiologically relevant concentrations of various SCFA, and histone acetylation state was assayed by acid-urea-triton-X gel electrophoresis and immunoblotting.

Growth and apoptotic effects were studied by flow cytometry, and differentiation effects were assessed using transient transfections and Northern blotting.

Propionate C3 and valerate C5 caused growth arrest and differentiation in human colon carcinoma cells. The magnitude of their effects was associated with a lesser degree of histone hyperacetylation compared with butyrate. Acetate C2 and caproate C6 , in contrast, did not cause histone hyperacetylation and also had no appreciable effects on cell growth or differentiation.

Butyrate also significantly increased apoptosis, whereas the other SCFA studied did not. The growth arrest induced by the SCFA was characterized by an increase in the expression of the p21 cell-cycle inhibitor and down-regulation of cyclin B1 CB1.

These data suggest that the antiproliferative, apoptotic and differentiating properties of the various SCFA are linked to the degree of induced histone hyperacetylation.

Furthermore, SCFA-mediated growth arrest in colon carcinoma cells requires the p21 gene. Since butyrate is expected to impact cellular metabolic pathways in colon cancer cells, we hypothesize that it could exert its antiproliferative properties by altering cellular metabolism.

We show that although Caco2 colon cancer cells oxidized both butyrate and glucose into CO2, they displayed a higher oxidation rate with butyrate as substrate than with glucose. Furthermore, butyrate pretreatment led to an increase cell capacity to oxidize butyrate and a decreased capacity to oxidize glucose, suggesting that colon cancer cells, which are initially highly glycolytic, can switch to a butyrate utilizing phenotype, and preferentially oxidize butyrate instead of glucose as energy source to produce acetyl coA.

Butyrate pretreated cells displayed a modulation of glutamine metabolism characterized by an increased incorporation of carbons derived from glutamine into lipids and a reduced lactate production. The butyrate-stimulated glutamine utilization is linked to pyruvate dehydrogenase complex since dichloroacetate reverses this effect.

Furthermore, butyrate positively regulates gene expression of pyruvate dehydrogenase kinases and this effect involves a hyperacetylation of histones at PDK4 gene promoter level. Our data suggest that butyrate exerts two distinct effects to ensure the regulation of glutamine metabolism: As a product of fermentation within the human colon, it serves as the most important energy source for normal colorectal epithelium.

It also promotes the differentiation of cultured malignant cells. A switch from aerobic to anaerobic metabolism accompanies neoplastic transformation in the colorectum.

The separate functional roles for n-butyrate may reflect the different metabolic activities of normal and neoplastic tissues. Relatively low intracolonic levels of n-butyrate are associated with a low fibre diet. Deficiency of n-butyrate, coupled to the increased energy requirements of neoplastic tissues, may promote the switch to anaerobic metabolism.

The presence of naturally occurring differentiating agents, such as n-butyrate, may modify the patterns of growth and differentiation of gastrointestinal tumours. This study aims to assess the effects of butyrate on inflammation and oxidative stress in subjects with chronically mildly elevated parameters of inflammation and oxidative stress. Before and after the intervention feces, blood and colonic mucosal biopsies were obtained. Parameters of antioxidant defense and oxidative damage, myeloperoxidase, several cytokines, fecal calprotectin and CRP were determined.

Although in general butyrate did not affect colonic glutathione levels, the effects of butyrate enemas on total colonic glutathione appeared to be dependent on the level of inflammation. The current article adds to this discussion but does not definitively answer the question.

Overall, the data suggest that in the absence of a known fibrostenotic stricture with obstructive symptoms, a high fiber diet is likely safe in patients with IBD and may impart a weak benefit.

Yet, answering these clinically relevant questions with more confidence and detail is within our grasp. The advent of e-cohorts offers the potential to transform research in the future by allowing investigators to design cost-efficient Web-based clinical studies, particularly for interventional environmental clinical trials. Short-chain fatty acids SCFAs are produced in the colon by the fermentation of dietary carbohydrates and fiber polysaccharides and have been shown to stimulate mucosal-cell mitotic activity in the intestine.

This study compared the effects of an intravenous and an intracecal infusion of SCFAs on the small-bowel mucosa. Standard TPN produced significant atrophy of the jejunal and ileal mucosa.

The intravenous and intracolonic infusion of SCFAs were equally effective in inhibiting small-bowel mucosal atrophy. Since then, butyrate enemas have popularly been used as medicaments stemming from their potential to impart beneficial attributes to the colon. This potential involves an increase in mechanical strength of injured colonic mucosa to hasten the healing process Bloemen et al.

Much as butyrate tends to impart a protective effect, several authors have indicated failures or limited success of butyrate to relieve IBD patients Harig et al. This is done mainly through intrarectal administration of enemas that contain butyrate. The procedure is one of the earliest approaches to treat UC even in patients who had been unresponsive to or intolerant of standard therapy Scheppach et al. The intrarectally administered butyrate needs to be absorbed before it works.

Normally butyrate absorption mainly occurs in proximal colon whose function is impaired during UC. This hinders absorption of topically administered butyrate and may not benefit UC patients.

However, butyrate absorption in the colon can be increased by manipulating electrolyte composition in the rectal lumen Holtug et al. Thus, topical butyrate, given intrarectally in form of SB, plays a double role; firstly by employing sodium ions, it accelerates rectal absorption of SB and secondly, the absorbed butyrate imparts healing to the colonocytes.

The end result is epithelial proliferation to restore the damaged epithelium, especially the lost colonic epithelial continuity. To the best of our knowledge, this finding has not been reported before. However, the systemic effect of butyrate to other body systems and organs has been reported. All these facts and our own study affirm that butyrate has a potential to impart protective roles to various body organs and systems through systemic administration.

Consistent with this theme, we recently reported that in mice, compositionally defined diets that are made with purified ingredients and lack fermentable fiber promote low-grade inflammation and metabolic syndrome, both of which could be ameliorated by supplementation of such diets with the fermentable fiber inulin. However, in contrast to the case of low-grade inflammation, addition of inulin, but not the insoluble fiber cellulose, further exacerbated the severity of colitis and its associated clinical manifestations weight loss and bleeding in both low- and high-fat diets.

However, the purpose of autophagy is not the simple elimination of materials, but instead, autophagy serves as a dynamic recycling system that produces new building blocks and energy for cellular renovation and homeostasis. Here we provide a multidisciplinary review of our current understanding of autophagy's role in metabolic adaptation, intracellular quality control, and renovation during development and differentiation.

We also explore how recent mouse models in combination with advances in human genetics are providing key insights into how the impairment or activation of autophagy contributes to pathogenesis of diverse diseases, from neurodegenerative diseases such as Parkinson disease to inflammatory disorders such as Crohn disease. These amino acids can subsequently be used by the microbiota in the colon, or transported from the lumen into the portal blood stream.

In addition, the host itself produces substrates such as glycoproteins e. This higher rate of bacterial protein fermentation has been related to high pH and low carbohydrate availability in the large intestine [22].

The preferred amino acid substrates of colonic bacteria include lysine, arginine, glycine, and the BCAA leucine, valine, and isoleucine [32], resulting in the generation of a complex mixture of metabolic end products including among others ammonia, SCFA acetate, propionate, and butyrate , and branched-chain fatty acids BCFA; valerate, isobutyrate, and isovalerate.

Intestinal barrier function is significantly less developed in full-term newborn piglets receiving total parental nutrition compared with those receiving enteral nutrition 7. Production of SCFA in the bowel may be crucial for gastrointestinal adaptation and maturation in the early stage of postnatal life 8. To test the hypothesis that SCFA may originate from polypeptides as well, the production of these acids from albumin and specific amino acids was examined in a faecal incubation system.

Albumin was converted to all C2-C5-fatty acids, whereas amino acids generally were converted to specific SCFA, most often through the combination of a deamination and decarboxylation of the amino acids, although more complex processes also took place. This study indicates that a part of the intestinal SCFA may originate from polypeptides, which apparently are the major source of those SCFA isobutyrate, valerate, and isovalerate only found in small amounts in the healthy colon. Moreover, gastrointestinal disease resulting in increased proteinous material in the colon exudation, mucosal desquamation, bleeding, and so forth may hypothetically influence SCFA production.

The present study was undertaken to assess the metabolic performance of the mucosa in UC and especially to explore whether a metabolic abnormality could be detected. To facilitate this approach a method of preparing suspensions of colonocytes was devised. Mucosa of the distal colon depended metabolically mostly on n-butyrate, whereas the proximal colonic mucosa depended mostly on glucose and glutamine for respiratory fuel.

Production of 14C02 was linear whenever this could be tested for 60 min. The diminished production of ketone bodies mirrors the decreased oxidation of butyrate to CO2. Ketogenesis was significantly lower in the quiescent-colitis group than the control group and lower still in the acute-colitis group. Butyrate oxidation to C02 and ketone bodies was significantly impaired, and the impairment correlated with the acute or chronic involvement of the mucosa. Glucose oxidation was increased. Glutamine oxidation was increased.

Metabolic products, 14CO2, acetoacetate, beta-hydroxybutyrate and lactate, were measured and injury to cells was judged by diminished production of metabolites.

Oxidation of n-butyrate to CO2 and acetoacetate was reduced at 0. To bypass short-chain acyl-CoA dehydrogenase activity necessary for butyrate oxidation, ketogenesis from crotonate was measured in the presence of 1.

Suppression by sulphide of ketogenesis from crotonate Methionine equally improved CO2 and ketone body production, suggesting a global reversal of the action of sulphide. Sulphide-induced oxidative changes closely mirror the impairment of beta-oxidation observed in colonocytes of patients with ulcerative colitis. A hypothesis for the disease process of ulcerative colitis is that sulphides may form persulphides with butyryl-CoA, which would inhibit cellular short-chain acyl-CoA deHydrogenase and beta-oxidation to induce an energy-deficiency state in colonocytes and mucosal inflammation.

Because the intravenous route may have wider clinical application, we studied the effect of intravenous n-butyrate on the mechanical strength of colonic anastomoses in the rat.

On the fifth postoperative day, bursting pressure and bowel wall tension of the anastomoses were measured in situ. Anastomotic tissues were analyzed for hydroxyproline. Tissue hydroxyproline was not different between the two groups TPN, The enteral or parenteral provision of glutamine and acetoacetate has been shown to be trophic to both small and large intestinal mucosa Fox et al.

Butyrate has diverse and apparently paradoxical effects on cellular proliferation, apoptosis and differentiation that may be either pro-neoplastic or anti-neoplastic, depending upon factors such as the level of exposure, availability of other metabolic substrate and the intracellular milieu. In humans, the relationship between luminal butyrate exposure and CRC has been examined only indirectly in case-control studies, by measuring fecal butyrate concentrations, although this may not accurately reflect effective butyrate exposure during carcinogenesis.

Perhaps not surprisingly, results of these investigations have been mutually contradictory. The direct effect of butyrate on tumorigenesis has been assessed in a number of in vivo animal models, which have also yielded conflicting results. In part, this may be explained by methodological differences in the amount and route of butyrate administration, which are likely to significantly influence delivery of butyrate to the distal colon.

Nonetheless, there appears to be some evidence that delivery of an adequate amount of butyrate to the appropriate site protects against early tumorigenic events. Future study of the relationship between butyrate and CRC in humans needs to focus on risk stratification and the development of feasible strategies for butyrate delivery.

However, cell surface receptors have been identified for butyrate; these receptors, GPR43 and GPRA also known as hydroxycarboxylic acid receptor 2 or HCA2 , are G protein coupled and are expressed in colonic epithelium, adipose tissue, and immune cells Blad et al.

In colonic lumen, butyrate is generated at high concentrations 10—20 mM by gut microbiota and serves as an endogenous agonist for GPRA Thangaraju et al.

We have shown that Gpra expression in colon is induced by gut microbiota and is downregulated in colon cancer Cresci et al. Gpra in immune cells plays a nonredundant function in niacin-mediated suppression of inflammation and atherosclerosis Lukasova et al.

Gut microbiota also produce niacin. Niacin deficiency in humans results in pellagra, characterized by intestinal inflammation, diarrhea, dermatitis, and dementia Hegyi et al. It is of great clinical relevance that lower abundance of GPRA ligands niacin and butyrate in gut is associated with colonic inflammation. For this, we first depleted gut microbiota with antibiotics, which reduces the production of butyrate, the endogenous agonist for GPRA.

Consistent with increased inflammation, we found that antibiotic treatment increased the number of polyps 8. We then tested whether administration of niacin protects antibiotic-treated mice against colonic inflammation and carcinogenesis. Niacin was added to drinking water along with antibiotic cocktail. The present studies identify Gpra as an important mediator of butyrate effects in colon and also as a critical molecular link between colonic bacteria and dietary fiber and the host.

When we first met the patient he reported bilateral pain and swelling of the knee, frequent episodes of fever and night sweats as well as fatigue. We offered the paleolithic ketogenic diet along with close monitoring of the patient. The patient started the diet on 4 January The diet is consisting of animal fat, meat, offal and eggs with an approximate 2: Red and fat meats instead of poultry as well as regular intake of organ meats from pork and cattle were encouraged.

Grains, milk, dairy, refined sugars, vegetable oils, oilseeds, nightshades and artificial sweeteners were excluded. Small amount of honey was allowed for sweetening. The patient was not taking any supplements. Regular home monitoring of urinary ketones indicated sustained ketosis. Regular laboratory follow-up was used to monitor the course of the disease as well as for giving feedback how to fine tune the diet.

The patient was under our close control and gave frequent feedbacks and so we could assess the level of dietary compliance. The patient maintained a high level dietary adherence on the long-term, yet on his birthday, he made a mistake: Clinical consequences are discussed later.

From July onwards he also consumed small amounts of vegetables and fruits. Given the persistence of certain alterations in laboratory values mild anemia on 10 November , despite 10 months on the paleolithic ketogenic diet, we suggested to tighten the diet again.

From this time on he did neither consume vegetables and fruits nor vegetable oil containing spices such as cumin and cinnamon. Currently, he is without medicines for 15 months. The knee pains of the patient began to lessen at 4th week on the diet and completely disappeared by the third month. From this time onwords he regularly went to school by bike 20 km daily.

He reported restored energy and increased physical and mental fitness. Although during the eight months before diet onset his weight was declining, following diet onset he began to gain weight. At 12 months after diet onset, his height was cm and weighted 50 kg BMI: The change in his height and weight is depicted in Figure 5.

At the time of writing the article he is on the diet for 15 months and is free of symptoms as well as side effects. Intraperitoneal injection is used for small species for which intravenous access is challenging and it can be used to administer large volumes of fluid safely Table 1 or as a repository site for surgical implantation of a preloaded osmotic minipump. Absorption of material delivered intraperitoneally is typically much slower than for intravenous injection.

Although intraperitoneal delivery is considered a parenteral route of administration, the pharmacokinetics of substances administered intraperitoneally are more similar to those seen after oral administration, because the primary route of absorption is into the mesenteric vessels, which drain into the portal vein and pass through the liver.

In addition, a small amount of intraperitoneal injectate may pass directly across the diaphragm through small lacunae and into the thoracic lymph. Good reviews of studies investigating the influence of diet on butyrate-producing bacteria exist 11 and 34 and suggest that plant-derived polysaccharides such as starch and xylan, as well as cross-feeding mechanisms with lactate-producing bacteria, are the main factors governing their growth. Our metagenomic analysis supports the acetyl-CoA pathway as the main pathway for butyrate production in healthy individuals Fig.

However, the detection of additional amino acid-fed pathways, especially the lysine pathway, indicates that proteins could also play an important role in butyrate synthesis and suggests some flexibility of the microbiota to adapt to various nutritional conditions maintaining butyrate synthesis. Whether the prevalence of amino acid-fed pathway is associated with a protein-rich diet still needs to be assessed. It should be noted that those pathways are not restricted to single substrates, as displayed in Fig.

Furthermore, the acetyl-CoA pathway also can be supplied with substrates derived from proteins either by cross-feeding with the lysine pathway as discussed above or by direct fermentation of amino acids to acetyl-CoA However, whereas diet-derived proteins are probably important for butyrate synthesis in the ileum, where epithelial cells use butyrate as a main energy source as well 36 , it still needs to be assessed whether enough proteins reach the human colon to serve as a major nutrient source for microorganisms.

Another possible colonic protein source could originate with lysed bacterial cells. Detailed investigations of butyrate-producing communities in the colon of carnivorous animals will add additional key information on the role of proteins in butyrate production in that environment.

Several butyrate-producing organisms do specifically colonize mucus 37 , and for some, growth on mucus-derived substrates was shown Intact proteins that escape the small intestine or produced in the large intestine mucus, cells, microbial proteins are digested further in the large intestine by bacterial enzymes and the surviving pancreatic proteases and peptidases 35, This protein degradation has been reported to be highest in the distal large intestine and is m ost likely related to the pH in the different regions The di gested proteins can be used by the microbiota, which produce several metabolites such as SCFAs, ammonia, and amines.

These metabolites may be linked to several health outcomes Both small and large intestinal microbiota are capable of synthesizing AAs, and absorption of microbial AAs has been demonstrated to take place in the intestine. The brain requires a lot of energy The brain runs on glucose The need for dietary glucose is particularly acute in fetuses The cooking of starch allowed us to get that energy Some modern HGs make significant use of exogenous glucose We have many more copies of amylase than other primates Some of us have developed persistent lactase We are hard wired to love sweetness Yes, the brain requires a lot of energy; no it does not have to come from dietary glucose I agree wholeheratedly that our brains require a lot of energy, much more than other organs, and that our needs are many times more acute than in other primates.

Fetal and infant growth does not depend on dietary glucose Brand-Miller also insists that "The fetus grows on the mother's maternal blood glucose. The evolutionary argument Since our brain energy needs are met perfectly well with either a high glucose intake or a low glucose intake, it cannot be reasonable argued that our large brains must have developed under conditions of high glucose intake. Persistent adequate availability of the predominant energy source and essential micronutrients For the exogenous glucose condition to have been the predominant evolved state, we would have required a consistent source of exogenous glucose on a regular basis, year round, for multiple generations.

For the endogenous glucose condition to have been the predominant evolved state, we would have required a consistent source of exogenous fat and protein on a regular basis, for multiple generations.

If the energy source were dietary glucose, we would require: If the energy source were dietary fat and protein, we would require: What can we conclude from the diets of modern hunter-gatherer societies? Why do we have more copies of amylase than other primates? Some populations have extended lactase production I think this supports more use of animal based nutrition than a need for sugar in particular.

Hard wired to love sweetness The hard-wired response to the taste of sweet is important and interesting, but I think it shows that sugar was rare, not a staple. Craving is different from hunger. Relatedly, there seems to be no satiety mechanism for sweet.

Evidence supporting endogenous glucose rather than exogenous as our evolved default In contrast to other species we have studied, humans stay in ketosis even when they have substantially more protein than basic needs require. References [1] From the ape's dilemma to the weanling's dilemma: S16, SS "This article explores a conception of the origins of fire as a process of shifting human interactions with fire, a process that, in a sense, still continues today. A survey of the association between mammal body size and the current threat of human hunting showed that large-bodied mammals are hunted significantly more than small-bodied species Lyons et al.

Studies of Amazonian Indians Alvard and Holocene Native American populations in California Broughton , Grayson show a clear preference for large prey that is not mitigated by declines in their abundance. After studying California archaeological sites spanning the last 3. The human hunters switched from large mammal prey highly ranked prey to small mammal prey lower-ranked prey over this time period figure 7.

Grayson stated that there were no changes in climate that correlate with the nearly unilinear decline in the abundance of large mammals. Looking further back in time, Stiner and colleagues described a shift from slow-moving, easily caught prey e. Amber O'Hearn at If ketosis is like fasting, we had better use it carefully, judiciously, and sparingly.

Ketosis is normally indicative of the fasting state Many believe that staying in either phase prolongedly leads to disease. Diabetes May , 54 5 ] But hold on. Dogs are in many ways similar to humans. Our digestive anatomy and physiology is very similar. They keep their bodies and their brains going by increased glucose. The next few slides summarise topics I've spoken and written about before. Please see Optimal Weaning from an Evolutionary Perspective for more details and links about brain growth and our acquired reliance on meat during evolution.

Brains take a lot of energy to run, To accommodate that we made a trade. I would almost like to call a ketogenic diet a brain-growth mimicking diet. Graphic from [Cah] On a high carb diet, you might need to fast to attain an enlightened brain state.

References In the interest of time, I did not do my usual practice of end-to-end citations. Ketone body transport in the human neonate and infant. Schugar, and Peter A.

A comparison of ketosis in man and dog. March 1, The Journal of Biological Chemistry. Frontiers in Molecular Neuroscience. Changes in brain weights during the span of human life: Quantitative growth and development of human brain.

Stacpoole, and Mark L. Robert Thompson, Lorne E. Haworth, Susan Phillips, Alicia Chan, et al. Haney, and Zahava Turner. Results, Insights, and Future Directions. A Case Report and Review of the Literature. Developmental changes of cerebral ketone body utilization in human infants. Hoppe Seylers Z Physiol Chem. Diet and the performance of racing sled dogs.

J Am Vet Med Assoc. S27 January 1, Myers Diet composition modifies the toxicity of repeated soman exposure in rats. Epub Mar Tiwari, and Bert B. Human brain evolution in an ecological context. Noebels, Massimo Avoli, Michael A. Olsen, and Antonio V. Does the Protein-to-Energy Ratio Matter? Proposed Mechanisms of Action. Evidence for an Unidentified Regulatory Component of the System. The pattern of blood lipids, glycerol and ketone bodies during neonatal period, infancy and childhood.

Acta Paediatr Scand Jul;55 4: El-Mallakh The ketogenic diet for type II bipolar disorder. Frontiers in Endocrinology, 4, The Journal of Nutrition [01 Apr , 4: Fenton, and Phillip Stafford. Insights from Genetic Profiling. Ketone body metabolism in the mother and fetus. Tenuous arguments from fibre apologists According to many plant-eating enthusiasts, we must eat fibre to be healthy for the following reasons: Fibre is the only way to get butyrate.

Butyrate prevents colon cancer. Butyrate in the colon treats colitis. Butyrate is the preferred fuel of the colonocyte, therefore it is essential.

Without butyrate your colon cells will die off. Anecdotes such as the " Crohn's Carnivore " suggest a different solution might hold for some: Now I have a perfectly normal colon. If those two events are indeed correlated, and someone could figure out exactly how, a whole lot of people would be able to find relief from a terrible disease. Such a diet may first sound restrictive but our previous experience indicate that a full fat-meat diet is needed in the most severe cases of Crohn's disease.

In addition, our experience shows that even a single occasion of deviation from diet rules may result in lasting relapse. This was the case in the present patient too where breaking the strict rules eating the "paleo cakes" resulted in a thickening of the bowel wall.

Based on our experience this is due to the components of the popular paleolithic diet including coconut oil, oil seeds and sugar alcohols which may trigger inflammation.

From a press release: At least one research group agrees with my speculation that the interior metabolites may be important for the effect [Siv] " "As the cell-surface receptors for SCFAs are located on the lumen-facing apical membrane of colonic epithelial cells see below , the luminal concentrations of these agonists are physiologically relevant. In any case, we certainly do generate butyrate in the absence of dietary fibre.

The amount of vitamin B-6 you need increases as you get older. Eat chicken, fish, potatoes and fruit to meet your vitamin B-6 needs. Thank you for your question! One way to pick a vitamin supplement brand is to look for one that has the USP designation on the label. Supplements that are verified by the United States Pharmacopeia USP have met standards of quality, purity, potency, performance, and consistency and are made with current FDA good manufacturing practices.

Multivitamins that are marketed to seniors or adults over 50 years old usually contain more calcium and vitamins D and B12 with less iron. Seniors are commonly deficient in vitamin D, for example. And of course, try to get most of your nutrients from healthy foods, such as whole grains, fruits and vegetables, nuts and seeds and lean meat, poultry and fish.

Thanks for sharing the details. You are spot on. The number of calories needed may vary based on sex, weight, or age. I think you need to be more specific. Hi Susan, thank you for bringing this up!

There are many drug-nutrient interactions that are not mentioned here. There are also some good resources out there on the topic. Food Medication Interactions 18th Edition. No doubt that your suggestions are very good. But what is the dietary suggestions for an Indian who is pure vegetarian? That is a great question, thank you for bringing it up! For nutrition guidelines specific to Indians, the Food and Agriculture Organization of the United Nations has a dedicated webpage, as well as the downloadable Dietary Guidelines for Indians — A Manual.

These should get you started! Hi Larry, are you inquiring about a B vitamin? Since you have multiple medical conditions and are on medications, I would run this by your doctor. These nutrients help keep your nervous system healthy, your metabolism […].

It gives me 3, calorie burn a day. Thanks for your question. We would advise checking in with Fitbit to see what they think about your rate of calorie burning. So, yes, that does seem high for a 2. You can try looking at other sites like this to calculate your calorie burn: Great job and keep it up!

Careers Careers at Shield Open Positions. Customer Rights Customer Rights. Shipping Shipping Info Returns. Retail Customers Retail Login. Calories The amount of calories you need depends on how physically active you are. A sedentary male over the age of 70 requires around 2, calories.

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