Tag Archives: inflammation

Nanoparticles and gut effects – generally recognized as safe?

Models for oral uptake of nanoparticles in consumer products

Titanium dioxide nanoparticle ingestion alters nutrient absorption in an in vitro model of the small intestine

Zhongyuan Guo, Nicole J. Martucci, Fabiola Moreno-Olivas, Elad Tako, Gretchen J. Mahler. Titanium dioxide nanoparticle ingestion alters nutrient absorption in an in vitro model of the small intestine. NanoImpact, 2017; 5: 70 DOI: 10.1016/j.impact.2017.01.002

In the study above, researchers took a meal’s worth of titanium oxide nanoparticles — 30 nanometers across — over four hours (acute exposure), or three meal’s worth over five days (chronic exposure) and determined the effect on the gut. Acute exposure caused no harm,  but chronic exposure diminished the absorptive projections on the surface of intestinal cells called microvilli. With fewer microvilli, the intestinal barrier was weakened, metabolism slowed and some nutrients — iron, zinc, and fatty acids, specifically — were more difficult to absorb. Enzyme functions were negatively affected, while inflammation signals increased. It turns out that nanoparticles are everywhere, especially in food, cosmetics, and pharmaceuticals. It can enter the digestive system through toothpastes, since Titanium dioxide is used to create abrasion needed for cleaning. The oxide is also used in some chocolate to give it a smooth texture; in donuts to provide color; and in skimmed milks for a brighter, more opaque appearance which makes the milk more palatable. Dunkin Donuts stopped using powdered sugar with titanium dioxide nanoparticles in 2015 in response to pressure from the advocacy group As You Sow.

http://www.binghamton.edu/us/story/417/food-additive-found-in-candy-chewing-gum-could-alter-digestive-cell-structu

There is emerging evidence that we have generated strategies to utilise nanoparticles for dietary and physiological benefit evolutionarily.  Thus, nanoparticulate structures are neither inherently toxic nor inherently safe: like all molecules these decisions will rest upon molecular structure, biological environment, degree of exposure and host susceptibility.

Nanoparticues act in a number of wasy internally, especially in the gut lumen, where they are exposed to mucin, proteins, pH changes, and other existing charged particles. There has been described a protein coating of nanoparticle surfaces, referred to as a ‘corona’, this phenomenon has been known for decades and will inevitably happen in the particle’s native environment. In the gastrointestinal tract it is likely that the acidic pH of the stomach, which mainly is maintained even postprandially, and the presence of gastrointestinal enzymes, will serve to denude ingested particles of their surface-adsorbed molecules but then re-adsorption of novel entities will occur in the less acidic small bowel lumen.

There are many exogenous inorganic particles are man-made particles comprising titanium dioxide or silicates/aluminosilicates. Titanium dioxide (designated E171 in Europe) is used for whitening and brightening foods, especially for confectionary, white sauces and dressings, and certain powdered foods.

Titanium dioxide (designated E171 in Europe) is used for whitening and brightening foods, especially for confectionary, white sauces and dressings, and certain powdered foods. It is also used in the pharmaceutical industry as an opacity agent. Titanium dioxide is typically found in gut tissue in the anatase polymorphic form and is a 100-200 nm diameter spherical particle that is resistant to gastrointestinal degradation. Particulate silicates and aluminosilicates (E554, E556 and E559 in Europe) are used in the food industry as anti-caking agents and to allow the flow of powders, and some are present in cheeses, sugars and powdered milks. In the UK, the major five food sources of particulate silicates are salt, drinking powders, chewing gum, instant pot savory snacks and icing sugar.Overall, intake of dietary inorganic microparticles in the UK has been estimated to be about 40 mg/person/day (35 mg for the silicates and 5 mg for titanium dioxide) which equates to a staggering daily exposure of 101214 particles/person.

How are  the partciles taken up in the gut? M-cell-uptake (transcytosis) at the surface of intestinal lymphoid aggregates is the quintessential pathway for gut particle uptake and is very well described, especially for large nanoparticles (20-100 nm) and small microparticles (100-500 nm). Hydrophobic particles appear to be much better taken up than hydrophilic particles,  and  generally, small particles are better taken up than large ones with, perhaps, an optimal size of around 50 nm diameter.

Other sources of nanoparticles (NM) relevant for oral exposure comprise mainly cosmetics (sunscreen, lipsticks, skin creams, toothpaste) and food (packaging, storage life sensors, food additives, juice clarifiers). Whereas NMs in food are intended to be ingested, nanoparticles for instance in cosmetics and ingredients in food packaging may accidently get into the gastrointestinal tract. Major materials used in these products are: silver, and metal oxides of zinc, silica, and titanium. Nanosilver (Ag) is used in food packaging. According to the Woodrow Wilson Nanotechnology Consumer Products Inventory 2011, Ag nanoparticles are the most commonly used new NM in consumer products followed by TiO2, ZnO, platinum (Pt) and silicium oxide NMs (http://www.nanotechproject.org/inventories/consumer/). Although gold NMs are also used in cosmetics, food packaging, beverage and toothpaste their main applications are in the medical field.

Decrease of particle size in the nanoscale has been identified as a main parameter for the increased toxicity of different materials. Polystyrene, for instance, is a very biocompatible polymer used in cell culture. Nanoparticles, however, made from this material are cytotoxic.

Compared to other metal and metal oxide nanoparticles intake of TiO2 by food is relatively high at 5 mg TiO2/person/d .Metal and metal oxide nanoparticles can accumulate in plants  and in animals of the food chain. That is worrisome.

A number of factors effect uptake of particles by the gut. Even in healthy individuals gastrointestinal transit is by far not constant and shows considerable variation through the large intestine . These effects are known to influence oral bioavailability of conventional drugs but are even more important for the effects of NMs because NMs readily adsorb proteins. Mucus represents an efficient acellular barrier. Mucus consists of mucin proteins (highly glycosylated extracellular proteins with characteristic gel-forming properties), antiseptic proteins (lysozyme) and other proteins (lactoferrin), inorganic salts and water. The major functions are the protection and the lubrication of the underlying tissue. The saliva, which is produced by the salivary glands, mainly consists of water (up to 99.5%), inorganic salts, proteins, and mucins. The high molecular weight mucin MG1 can bind to the surface of the epithelium and build the so-called mucus layer, displaying the acellular barrier of the oral cavity The mucus of the following parts, stomach and small and large intestine, is mainly produced by intraepithelial cells, and hickness increases from proximal to distal parts of the small and large intestine . Depending on the method used for the determination, the thickness of the mucus layer shows marked variation..The characteristics facilitating the passage through human mucus are relatively well known: electrostatic repulsion from negatively charged sugar moieties favors the penetration of positively charged hydrophilic molecules; the passage of lipophilic compounds is slow. Viruses, like the Norwalk virus with a size of 38 nm and human papilloma virus with a size of 55 nm diffused in human mucus as rapidly as they do in water These findings suggest that the surface charge plays a crucial role in the transport rates of nanoparticles through a mucus layer

In addition to particle size, dose and duration of the exposure are important for the interpretation of the data. In addition to particle size, dose and duration of the exposure are important. There is  a size-dependent decrease of the uptake from 34% for 50 nm particles to 26% for 100 nm particles , and dose and duration of the exposure are also important for absorption and uptake of NM.

Changes in mucus composition induced by Ag nanoparticles (Jeong et al., 2010), polystyrene particles and diesel exhaust increased mucus permeability and permeation of small molecules by a factor of 5. Thus NM enter more quickly through disease barriers.

The adherence of polystyrene nanoparticles to inflamed colonic mucosa was much higher than to normal mucosa. Inflammation appears to increase uptake and permeation of NMs in vitro and in vivo. Inflammation caused by Yersinia pseudotuberculosis increases the uptake of 100 nm carboxyl polystyrene particles in cell monolayers and in intestinal biopsies. Other factors of absorption include pH and thickness of the mucus layer, the gastrointestinal flora and in gastrointestinal passage time (motility)

Whereas plasma membranes restrict the cellular access for metal ions like silver cations, silver nanoparticles were readily internalized and intracellular silver concentrations were much higher than for silver ions. Studies for uptake and toxicity should, therefore, include AgNO3 for silver nanoparticles (Trojan horse effect) or bulk material.. Absorption may also be altered by a changed metabolization by enterocytes. Polystyrene and silver particles have been shown to inhibit the activity of cytochrome P450 enzymes, of note

To avoid foods rich in titanium oxide nanoparticles you should avoid processed foods, and especially candy. This information may make one question if these NM have any impact on the surge of colitis seen ion the general poplulation? How about autoimmune diseases? How about general inflammation, for if NM damage the intestinal barrier, inflammation results and it’s attendant consequences.

 

http://www.nanotechproject.org/cpi/

Hidradenitis Suppurativa and inflammation –

Hidradenitis Suppurativa (HS)

Hidradenitis suppurativa
Scarring, inflammatory abscess, with small pock marks (SINUS TRACTS) commonly found in Hidradenitis Suppurativa
Hidradenitis suppurativa
Gross 🙁

HS is a chronic inflammatory skin disease associated with the formation of multiple abscesses, nodules, and scars in the apocrine gland-bearing areas. Sites that are affected include inguinofemoral (groin), axillary (arm pit) , perianal, gluteal (buttocks) , and submammary (breast) regions. Approximately 1-4% of the population is affected by this disorder. The apocrine (sweat) glands get occluded by hyperkeratotic (skin material) debris that produce follicles that rupture and cause inflammation.

The course of HS can vary from small pustules to inflammatory nodules, and in some cases become inflammatory, deep abscesses and draining sinus tracts. In other words,  an infected pock marked mess.

This disease is staged in to three categories with Stage 1 being basic abscesses without scarring and Stage 3 being the worst, having destroyed completely an area with multiple abscesses that can be interconnected and have sinus tracts (holes) connected to the skin surface.

For those with this disorder, wearing loose fitting clothes that don’t rub the areas involved, not pinching the lesions, wearing antiperspirants  but not applying perfumes to the area are helpful. Topical anti-bacterial cleansing with Triclosan-containing soaps will decrease bacterial colonization. Don’t scrub the area when washing as that will inflame the lesions more.

Primary treatment includes quitting smoking – which is highly associated with Hidradenitis Suppurativa. If you continue to smoke, don’t expect to get better. Also weight loss is important as 2/3 of those with HS are overweight. The HS may be due to elevated insulin levels, hormonal changes, and dietary problems in these individuals. Avoiding dairy and high glycemic loaded foods can decrease the disease.

Metformin, an anti-diabetic drug can be helpful in decreasing the HS disease burden. This is a result of the insulin-sensitizing effect of Metformin as it is believed that HS results, in part, from elevated insulin levels.

Treatment methods, after the basics listed above, include the use of Resorcinol, a chemical peeling agent, which as a 15% solution and applied twice a day, can improve the HS lesions and decrease pain and inflammation.

Also used are antibiotics, usually Doxycycline and minocycline first line, then Clindamycin if those are not helpful. Clindamycin mixed with Rifampin has been effective in 2/3 of patients with moderate disease.  Some physicians use a combination of Moxifloxacin, Rifampin, and Metronidazole with good success.

Dapsone, an antibiotic with immunomodulatory effect, has had effect in early stage disease.

Intralesional injection of steroids is another option for local treatment as a monthly injection over a period of three months or so. Occasionally surgery must be done or an incision and drainage when a large abscess forms.

Androgens can promote the development of HS. It has been found that drospirenone- (or norgestimate-) containing oral contraceptives with spironolactone ( a blood pressure medication with anti-androgen effects) has been helpful in women.

For patients who don’t want to quit smoking or cannot lose weight and for those who fail other medical therapies, anti-TNF (tumor necrosis factor) agents are effective and have been approved for use in HS.  The injected agent Infliximab was found to have a 50% reduction in severity score with most having improvement in pain and quality of life. Adalimumab was recently FDA approved for HS treatment but has been less effective. Whereas Infliximab is administered by weekly infusions, Adlimumab is given by subcutaneous weekly injections. The problems with the anti- TNF agents include risks for infection, heart failure, demyelinating disease, a lupus-like syndrome, and malignancy.

Oral retinoids such as acitretin and Isotretinoin have shown beneficial effect as well. Acitretin given as  0.6 mg/kg daily for 9 to 12 months showed highly effective in diminishing the disease, an effect that remained after the medicine was stopped, unlike with the biological agents, which have a higher relapse rate after discontinuance. Isotretinoin also has been effective in several studies with lower relapse after discontinuance. Both agents are highly teratogenic.

Systemic prednisone can decrease inflammation when given over 7-10 days at 40 mg a day. Cyclosporine has also been used as well.

Vitamin D3 supplementation at 300-6000 Units daily has been helpful in decreasing HS lesions in some individuals.

 Zinc salts have antiinflammatory and antiandrogenic properties.  Zinc Gluconate at 90 mg daily was very effective (36%) in significantly decreasing the inflammation of low grade HS, with beneficial effect in most who use zinc supplements.

What is interesting about Hidradenitis Suppurativa, is the inflammatory component of the disease. We know that the risk of the disease increases with obesity and cigarette smoking, which are also associated with elevated markers of inflammation themselves. Obesity is associated with elevated inflammatory markers and insulin levels, which appear to play a role in the genesis of HS as well as other diseases (i.e hypertension, fatty liver, diabetes, cancer, etc) In the article listed below, it was recognized that HS and the risk of it’s progression can be estimated by CRP levels, a marker of total body inflammation.  CRP is produced by the liver in response to IL-6, another inflammatory marker. This generalized inflammation affects multiple organ systems.

Correlation of inflammatory serum markers with disease severity in patients with hidradenitis suppurativa (HS)

The above study examined the use of CRP and white blood count (wbc) in estimating the risk of progression and inflammatory content of patients with various stages of HS.

The study found that CRP level and neutrophil counts are effective tools for assessing the extent of disease severity and grade of inflammation in patients with HS above and beyond the association of these inflammatory markers with coincidental comorbidities.   For example, obese patient have elevations in CRP and smokers have higher white blood cell counts, but this study showed that CRP and wbc independently predicted worse disease status in patients with HS. There was a significant correlation between these inflammatory serum markers and disease severity according to HS severity grading scale. The end finding is that CRP is a significant and independent predictor for severe disease activity of Hidradenitis Suppurativa.

What interests me about this disease is it’s associations with comorbidities. Smokers have little hope of remission of HS and HS is associated strongly with obesity. These same disorders are inflammatory in their own right. It is felt that the elevated levels of insulin and insulin resistance in obesity may play a role in worsening of HS. Obesity and the hormonal catastrophe associated with it is also associated with coronary heart disease, hypertension, fatty liver, and a host of other life-limiting diseases. So again, here is a disease process (HS) that is, in part, partially a creature of our own design – bad habits. If we could stop smoking and limit obesity, how much HS would really exist?

Correlation of inflammatory serum markers with disease severity in hidradenitis suppurativa

 

Here is a link to a dermatology page regarding HS:

http://drcamisasblog.com/

 

 

 

 

 

 

Insane Medicine – Inflammation as a cause of psychiatric conditions!

 

 

 

 

Clustering of Depression and Inflammation in Adolescents Previously Exposed to Childhood Adversity

http://www.sobp.org/files/public/BPS%20Press%20Release_Miller%20and%20Cole_FINAL.pdf   <<< Childhood Adversity Increases Risk for Depression and Chronic Inflammation

Insane medicine – Replace saturated fats in your diet with Vegetable oils (Linoleic acid) to lower cardiac risk!

Replacing saturated fat with vegetable oil is associated with lower coronary artery disease risk based in a study in Circulation recently released (Circulation. 2014;130:1568-1578).

  1. Exchanging 5% of consumed calories from saturated fat sources (red meat and butter) with foods containing linoleic acid (an n-g fatty acid that is polyunsaturated and found in vegetable oil, seeds, and nuts) can decrease coronary heart disease events by 9%. So swap out your saturated fat sources with polyunsaturated fat to help out your heart!
  2. Linoleic acid (polyunsaturated fat) intake was inversely associated with heart disease, such that the more linoleic acid taken in, the lower the risk of heart disease. At the best outcomes, there was a 15% lower heart-risk and 21% lower death rates in those who consumed the most linoleic acid sources.
  3. Replace butter, lard, and fat from red meat with liquid vegetable oils when you prepare and cook foods.  By replacing saturated fat in this way, total and LDL cholesterol is reduced.
  4. Sources of Linoleic acid (an omega-6 polyunsaturated fat) include: soybean, sunflower, safflower, and corn oil, as well as nuts and seeds.
  5. Fats have 9 calories per gram. Use 1.5-3 tablespoons of vegetable oil daily to get 5-10% of calories from linoleic acid (100-200 calories total) It is important to replace saturated fat with these sources of polyunsaturated fats (linoleic acid) and not just adding this to the total fat intake.
  6. Linoleic acid does not promote inflammation based on a neutral effect on inflammatory markers or arachidonic acid levels (which increase in inflammation).

Cooking oil examples:

Safflower oil – 78 % PUFA (Linoleic acid)

Sunflower oil – 69% PUFA (Linoleic acid)

Corn oil – 62%

Soybean oil  – 61 %

Peanut Oil  – 34%

Canola oil  – 29%

Lard – 12 %

Palm oil – 10%

Olive oil  – 9%

Butterfat  – 4%

Palm kernel oil  – 2%

Coconut oil – 2%

 

General notes about fats:

  • Greater intake of trans-fats (hyrogenated oil for example) relative to polyunsaturated fats (PUFA) is associated with higher cardiac risk. N-3 omega fatty acids and alpha-linoleic (ALA), also an n-3 fatty acid) are associated with good cardiac risk. Linoleic acid (LA) , an n-6 PUFA most commonly eaten in the Western diets, also has been shown to be beneficial in preventing cardiac risk, but less investigation had been done regarding this fatty acid. Linoleic acid reduces LDL levels, which is a positive effect for decreasing cardiac risk. LA can be elongated into arachidonic acid, which is inflammatory and thrombogenic (blood clot forming). Studies have shown that LA is in fact not pro-inflammatory in the body. It does not increase C-reactive protein . It also has no effect on other inflammatory marker such as cytokines, fibrinogen, soluble vascular adhesion molecules, plasminogen activator inhibitor type 1, or tumor necrosis factor-α.
  • There appears to be a linear response to increasing LA intake – as one takes in more LA, there is less coronary events (heart attacks) and less death! Thus n-6 fatty acids (Linoleic acid) has cardioprotective effects! Increasing LA intake by 5% led to 9% less coronary heart disease and 13% less death!
  • It had been assumed that LA is converted to arachidonic acid (AA), which is inflammatory. AA  is the main precursor of eicosanoids with inflammatory and thrombogenic properties, such as prostaglandin E2, thromboxane A2, and leukotriene B4. It has been found, however, that the conversion of LA to AA is tightly controlled in the body, thus there is no increase in inflammation.

 

Insane Medicine – Inflammation and it’s risks.

Inflammation in the body breaks it down over time. Inflammation results from and, in part, causes autoimmune disorders and atherosclerosis with subsequent coronary artery disease and stroke. There are many ways to measure levels of inflammation in the body, but none are sensitive or specific for any particular condition. Likewise, inflammatory markers don’t always point to a specific treatment, but rather the presence of a system that is in trouble and needs thorough evaluation.

  • Inflammatory risk can be determined, in part, by elevations in C-reactive protein (CRP) and fibrinogen, which are both made in the liver as a result of the influence of cytokines such as interleukin-Ib, Interleukin-6 (IL-6), and Tumor necrosis Factor- alpha (TNF). Fibrinogen increases can increase your risk of platelet aggregation (clots) which increase stroke and heart attack risk.
  • There is evidence that DHEA and fish oil can decrease cytokine levels and decrease inflammation. Vitamin K can suppress IL-6 especially and thus decrease inflammatory markers. Nettle leaf extract has been found to suppress TNF-alpha and IL-1b cytokines. Aspirin, green tea, ginko bilboa, garlic, and Vitamin E have been found to decrease platelet aggregation and help blood flow, helping to avoid strokes and heart attacks. Lower fibrinogen levels may decrease the risk of myocardial infarction. Increased vitamin A levels decrease fibrinogen levels. Olive oil and fish have had a similar effect. Niacin (1000 mg a day) and vitamin C (2000 mg a day) will decrease fibrinogen. Bromelain (2000 mg/day) and EPA/DHA from fish oil also have a beneficial impact as well.
  • Elevated homocysteine levels also represent a cardiovascular threat. Elevated homocysteine prevents fibrinogen breakdown by inhibiting tissue plasminogen activator. Ways to diminish homocysteine levels and it’s risk include vitamin B12, vitamin B6, and trimethylglycine (TMG).
  • So elevations of homocysteine will increase your heart attack and stroke risk. Trimethylglycing (TMG) methylates homocysteine and converts it to methionine and s-adenosylmethionine (SAMe). In this process, the body needs folate and vitamin B-12. Homocysteine can also be removed from the body by the transsulfuration pathway using a vitamin B-6 dependent cystathione synthase enzyme. Vitamin B6 is necessary for this, and in some individuals, they lack the ability to produce the active form of vitamin B-6 (pyridoxal-5-phosphate), in which case, pyridoxal-5-phosphate can be supplemented instead to lower homocysteine.
  • So vitamins and supplements that decrease homocysteine to help preserve cardiovascular health include: TMG (500 mg a day), folate (800 mcg a day), vitamin B12 (200 mcg a day), inositol (250 mg a day), zinc (30 mg a day), and vitamin B6 (100 mg a day).
  • C-reactive protein: an inflammatory risk marker that increases under the influence of cytokines IL-6, IL-1B, and TNF-alpha. When elevated, heart attack risk increases by over two-fold .Studies have found that the statin rosuvastatin (Crestor) can decrease CRP levels and the inflammatory risk of heart attacks. Also helpful are aspirin, vitamin E, nettle leaf extract, DHEA, and fish oil.

So here is a basic list of inflammatory markers and cardiovascular risk markers that should be followed:

  1. Fibrinogen
  2. CRP
  3. Homocysteine
  4. Iron
  5. Glucose
  6. Cholesterol (HDL and LDL and triglycerides)
  7. DHEA
  • Obesity is a risk marker for heart attacks and cancer. Why is this? Increased circulating insulin and insulin resistance causes increased fat conversion of glucose and increased fat deposition. The increased insulin causes certain cancer types to grow as well as it serves as a growth factor.
  • The keys to successful strategies for health besides weight loss, include:
  1. Blood pressure control
  2. Glucose control
  3. Decreased LDL cholesterol
  4. Increasing your healthy HDL cholesterol
  5. Decreasing inflammatory markers such as fibrinogen, CRP, homocysteine, and cytokines.

Exercise is important. Be certain to consult your doctor before starting any exercise regimen. Use and exercise every muscle, every day. Exercise increases blood flow and lymph drainage increases. It also builds strength and flexibility, as well as balance and decreased falling risk. You feel less depressed and have more energy.

  • Coenzyme Q10: (Ubiquinone) is beneficial for heart and brain functioning, as well as being a blood pressure lowering supplement. Cells need it for energy production in the mitochondria and deficiency is found in aging and a variety of degenerative disorders. Muscles and the brain have high numbers of mitochondria which need this supplement. Taken orally, CoQ10 is absorbed and incorporated into the mitochondria. As one ages, the body produces only half of what it should of this vital supplement. Dosing is 30-300 mg a day. Of note, statins (anti-cholesterol agent) destroy co Q 10, so it is very helpful to take co Q10 supplements while on any statin. There are studies demonstrating increased energy production in the brain and muscles with Co Q10 supplementation, and it has been noted that there is an antioxidant protective ability as well provided by coQ10. In fact, there is speculation that Parkinson’s disease may result, in part, by reductions of co Q 10 levels in the brain (35% less than normal controls) and that with supplementation, some patients with Parkinson’s disease have had diminished progression of the disorder. As we age, Parkinson’s disease becomes more common, and it may be due to mitochondrial dysfunction and oxygen free radical production due to co-Q10 deficiency which results in the loss of neurons, thereby producing Parkinson’s disease. There is suggestion that dosages of coQ10 up to 1200 mg a day (which has minimal side-effects) seems to diminish the progression of Parkinson’s disease in some patients. This may be a result of the preservation of mitochondrial function.

…more to be added soon!

Insane medicine: Pregnant mothers may need to watch their fat intake during pregnancy – it may affect their children!

Insane medicine - Fat mice get fat by eating fat diets. The effect damages their progeny.
Insane medicine – Fat mice get fat by eating fat diets. The effect damages their progeny.
  • The average American diet has 37% fat content. The recommended amount is 25-35% according to the 2010 dietary guidelines. Four studies have shown the bad impact that high fat consumption during pregnancy has on the fetus.
  • Mice fed 45 % fat diets during pregnancy demonstrated deficits in memory with higher anxiety and depression scores as well! What’s worse is there was epigenetic effect as well – the following generation of mice displayed memory loss and behavioral change as well. Here is the link: http://www.abstractsonline.com/Plan/ViewAbstract.aspx?mID=3527&sKey=f830412f-200d-4363-8e53-e8af37236afe&cKey=f00a8887-5be2-467f-a500-480d7b3bcac8&mKey=54c85d94-6d69-4b09-afaa-502c0e680ca7
  • A study in rats also showed that the mother’s diet, if high in saturated fat and branched chain amino acids(BCAA), would prime the microglia of their offspring. Microglia are the mmune cells of the brain and will secrete pro-inflammatory cytokines in the hippocampus (a learning center). Also high levels of BCAA compete with tryptophan transport across the blood brain barrier. When there is less tryptophan in the brain, the brain makes less serotonin which then results in anxiety! The pups were found to have depression and anxiety scores that were much higher than pups born to mothers who ate a more fat-restricted diet. Here is the link: http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=8d86b6b5-65d9-4dc4-9b97-53b5a5db4027&cKey=529d5e00-6f15-426c-8ee3-c9c61424e666&mKey=54c85d94-6d69-4b09-afaa-502c0e680ca7
  • Other studies demonstrated that a high fat diet in the pregnant mother causes the down-regulation of oxytocin systems in the brain of offspring and causes anxiety to be prevalant in the progeny. This effect does not occur in the pups of normal fed pregnant female rats. In this study it was found that the fewer numbers of oxytocin-positive neurons within the PVN (paraventricular nucleus), the more anxious the rats were as adults. Oxytocin projections to the brainstem acts as an appetite suppressant,  hence leading to overeating in the progeny of overfed pregnant females. Oxytocin also plays a role in maternal behaviors as well. Mother rats literally groom their daughters to be attentive or neglectful mothers themselves and this is associated with the presence of normal numbers of oxytocin projections. If a rat has fewer oxytocin projections, they will be neglectful parents more likely. Hence multiple pathways of brain function  may be affected in the young of a high-fat diet mother. Here is a link: http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=93a801db-9e49-4d58-b917-97948ec69a18&cKey=74611e5c-0fa7-4ff0-9276-b94be31da2df&mKey=54c85d94-6d69-4b09-afaa-502c0e680ca7
  • These effects also occur in primate studies as well – monkeys whose mothers are fed high fat diets have fewer dopamine projections to the nucleus accumbens ‘reward center’ of the brain. As a result, they have a reward deficiency when they eat food and don’t get satiated at a normal level of food. Rather, they  must take in more food to get the same amount of reward as another monkey that came from a normal-fed mother and had normal dopamine projections in the brain. Thus they get fatter.
  • Dietary guidelines recommend a diet of 25-27% fat. See this link for the recommendations of a standard diet:  http://www.health.gov/dietaryguidelines/dga2010/DietaryGuidelines2010.pdf  However, the average person takes in 37% fat or more!! See this link showing how much we really take in:  http://jn.nutrition.org/content/140/10/1832.long
  • We eat more than we think. We need to recognize that our food choices and stress patterns can affect our children through epigenetic mechanisms especially. We can set up our children for failure. These studies are done in standard models for humans and show the impact high fat diets in pregnancy  have on their children: Memory deficits, anxiety, depression, and future weight problems may echo the studies in rat and monkey populations.  The apple doesn’t fall far from the tree, for it seems that overweight parents have overweight children. Food for thought!!
  • http://fatmouse.org/

Insane medicine – Carrageenan – a frequently used additive with potential risk.

Carrageenan are polysacharrides created from edible seaweeds, used in food for gelling, thickening, and stabilizing.
Carrageenan are polysacharrides created from edible seaweeds, used in food for gelling, thickening, and stabilizing.

Moleculare_structure_of_different_carrageenan_types.svg

  • Carrageenans are polysacharrides created from edible seaweeds and used in food products where they provide gelling, thickening, and stabilizing effects. It has multiple uses.
  • There have been  concerns that it can cause inflammatory gut conditions, such as ulcerative colitis or colon cancer.There is no formal evidence that this occurs.
  • It is considered to be GRAS (generally recognized as safe). Certainly there is no reason to add this to your diet, but certainly avoid it if possible. Either was, it still has not been shown to be unsafe.

Insane Medicine – Probiotics for inflammation, gut health, antibiotic-associated diarrhea, and many other things!!

Insane Medicine - probiotics help!
Insane Medicine – probiotics help!
  • The symbiotic organisms found in the gut and elsewhere are called “probiotics.” These organisms help metabolize foods, absorb nutrients, prevent pathogenic colonization, and  help maintain intestinal health by living within our gut and competing with other unhelpful bacteria.
  • Some foods have probiotics added in them, such as: yogurt, kefir, kombucha tea, cheese, buttermilk, fermented cabbage like sauerkraut, and kimchi,  and acidophilus milk.
  • Lactobacillus species, Bifidobacteria species, and Saccharomyces boulardii are the most commonly used probiotic species used. Lesser probiotics include Streptococcus thermophilus 
  • Processed foods do not have live probiotic organisms. The processing kiolls the organisms. Look for labels that say “contains live active cultures.”
  • Probiotics work by competing with the growth of harmful bacteria in the gut by taking up space and nutrients. Siome produce antibacterial substances, such as hydrogen peroxide, acetic acid, or lactic acid, that prevents bacterial growth.
  • Probiotics appear to be immunomodulators,  stimulating lymphocyte and macrophage activity, reducing markers of intestinal inflammation such as tumor necrosis factor and alpha-1-antitrypsin. They can increase the secretion of immunoglobulin A in the gut against harmful bacteria.
  • Probiotics not only fight intestinal and urogenital pathogens, but they also are helpful for several conditions such as inflammatory bowel disease,  food allergy, pouchitis,  and as an adjuvant to vaccination.
  • Remember to use only proven blends of probiotics. Not all brands of probiotics are equivalent, even if they have the same agents in them!
  • Primary uses of Probiotics include uses for Antibiotic-associated diarrhea, Clostridium dificile infections, irritable bowel syndrome, and preventing respiratory infections.
  • The use of a probiotic with antibiotics can reduce diarrhea by 45 % or so.  Lactobacillus has the best evidence for success, with  Florajen ( Lactobacillus acidophilus) being very effective. Lactobacillus plantarum299v (ProViva) is also useful.
  • Bifidobacteriuminfantus and Bifidobacterium longus are effective as is Saccharomyces boulardii for reducing antibiotic-associated diarrhea.
  • Combination products such as Lactobacillus acidophilus LA-5 plus Bifidobacterium BB12 (AB-Yogurt), Bifidobacterium lactis plus Streptococcus thermophilus (Nan 2), and  Lactobacillus bulgaricus plus Streptococcus thermophilus plus Lactobacillus casei DN114401 (DanActive, Actimel) are also effective, reducing diarrhea by 40%.
  • Probiotics are also helpful for reducing the risk of Clostridium difficile infection in patients taking antibiotics. The combination of Lactobacillus acidophilus CL1285 plus Lactobacillus casei (Bio-K+Cl1285 is effective in reducing C. dificile infection when taking antibiotics by over 80 %.
  • Lactobacillus planarium299v (ProViva) can reduce recurrence of C. dificile infections. Saccaromyces boulardii(Florastor) also can reduce C. dificile infections by over 60%.
  • Combination products include Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus paracasei, Lactobacillus bulgaricus, and Streptococcus thermophilus (VSL#3) and DanActive/Actimel (Lactobacillus bulgaricus plusStreptococcus thermophilus plus Lactobacillus casei)
  • For irritable Bowel syndrome, Bifidobacterium infantis 35624 (Align or Bifantis Procter & Gamble) works well, decreasing abdominal complaints. The product, VSL#3, works well in decreasing IBS symptoms.
  • Probiotics also decrease respiratory infections by 30 % or more. Lactobacillus plantarum, Bifidobacterium longum, Bifidobacterium bifidum, Lactobacillus gasseri, and Streptococcus thermophilus are helpful in various combinations.
  • Avoid or be careful with probiotics if you are immunocompromised. Ask your doctor first before using them in that case.

Products you can use include:

  • Activia yogurt (Dannon –Bifidobacterium lactis), Align (Proctor and Gamble -Bifidobacterium infantis) for digestive health and antibiotic induced diarrhea.
  • Culturelle (ConAgra Foods – Lactobacillus GG) with multiple varieties,  It helps with digestion and decreases bloating sensation.
  • Danactive, with a mixture of probiotics in it, for antibiotic associated diarrhea.
  • Fllorajen (Lactobacillus acidophilus) with many varieties, useful for antibiotic-associated diarrhea and bowel health.
  • VSL#3(Sigma-Tau Pharmaceuticals – Lactobacillus acidophilus, L. plantarum, L. paracasei, L. bulgaricus, Bifidobacterium breve, B. infantis, B. longum, and Streptococcus thermophilus mixture) useful in inflammatory bbowel disorders and puchitis.
  • Fem-dophilus- Lactobacillus rhamnosus, for urinary health, preventing bacterial vaginosis and promoting vaginal health.
  • Probabclac and Lactinex are other agents used as probiotics with efficacy.

http://activia.us.com/  <—Activia probiotic

http://www.culturelle.com/culturelle-advantage?gclid=CJnP-YK9ocECFXLl7AodXm4AyQ  <—Culturelle

http://www.dannon.com/danactive/  <– Danactive

http://www.insyncprobiotic.com/?gclid=CNuBzaG9ocECFcNQ7AoduScA3A <–Probalac probiotic

http://www.jamiesonvitamins.com/5136  < –Jamieson probiotic sticks

http://www.florastor.com/  <–Florastor probiotics

http://www.vsl3.com/   <—vsl#3 probiotic

Insane Medicine – Inflammation and Aging – Mechanisms of poor aging!!

  • Inflammation affects the body in a number of ways, some we recognize physically and others not so much. For example, a cut on the skin can get red and inflammed. But there is a low grade, chronic inflammation that also occurs that increases as we age.
  • Many factors influence this inflammation, including genetics, lifestyle, and environmental agents. This can cause premature aging and disorders that accompany it, such as diabetes.
  • A study in the Canadian Medical Association Journal did suggest a link between elevated levels of Interleukin-6 (IL-6), a pro-inflammatory cytokine that when elevated, appears to drive other inflammatory marker up, such as CRP (C-reactive protein and fibrinogen).
  • IL-6 elevation appears to play a role in aging, causing people to age poorly when levels are elevated.
  • Successful aging is considered to have occured when an individual has good cardiovascular function ( no heart attacks) , good respiratory and musculoskeletal functioning (no emphysema/arthritis), and good mental well-being. In other words, there is an abscense of disability such as diabetes and severe arthritis or heart failure.
  • High levels of inflammation in the body are linked to cognitive decline (dementia and poor memory)
  • General body inflammation is involved in coronary artery disease, obesity, diabetes, chronic obstructive pulmonary disease (COPD), asthma, allergic conditions, rheumatoid arthritis, inflammatory bowel disease, and Alzheimer’s disease.
  • Inflammation can result in insulin resistance that then promotes obesity. Fat releases pro-inflammatory compounds that then worsens insulin-resistance. This results in a positive feedback cycle, making everything much worse.
  • Inflammatory markers being looked int incude tumopr necrosis factor (TNF), IL-6, C-reactive protein, prostaglandins, and leukotrienes. Elevations of these indicators reflects other conditions in the body, such as worsening arthritis.
  • In the Jupiter study, it was found that people with a nromal LDL (‘bad’) cholesterol would benefit from treatment with a statin to reduce the LDL even further if their CRP was elevated. The CRP elevation reflected an increased risk of heart attacks in these people despite normal or low cholesterol already. The statin (rosuvastatin), decreased the CRP and LDL cholesterol and ppears to decrease the risk of coronary events. Again, the elevated CRP reflects the inflammation in the coronary system, and this inflammation was improved by treatment with the statin.
  • Smoking worsens inflammation in the body and increases the risk of stroke and heart attacks. It promotes inflammation in the coronary arteries.
  • Obesity and high blood pressure also promote inflammation.

It is felt that IL-6 may be the driver of the inflammatory process, especially as increased levels of IL-6 (>2ng/L) increases mortality over three years. High IL-6 levels are associated with poor aging and increased risk of cardivascular events and death.

What to do:

  1. Eat a heart healthy diet including fatty fish, fruits, and vegetables. Include wine, tea, and chocolate, which have anti-inflammatory effects). The Mediterranean diet reduces inflammation.
  2. Avoid saturated fats, trans-fats, and refined sugar, which are pro-inflammatory.
  3. Get aerobic exercise. Being sedentary increases inflammation and pain.
  4. Lose weight  – obesity increases inflammation.
  5. Quit smoking.
  6. Take low dose aspirin if you had a prior heart attack.
  7. Take a statin if your docstor indicates a need. It helps inflammation and cholesterol.
  8. Don’t drink to excess.

Sleep at least 8 hours a day. AVoid stress, anxiety, depression through better coping mechanisms. Social isolation increases chronic inflammation.

http://www.cmaj.ca/content/185/16/E763.full.pdf+html?sid=f29c3195-e7d5-41f0-930f-adcbe22ac120

 

Other inflammatory markers:

Lipoprotein-associated Phospholipase A2) measures inflammation in the arteries –reference range: 81–259 ng/mL – below 200 is consistent with reduced risk of heart attack or stoke.