The immune system and CR. Methods to enhance resistance to infection.
We all die of something, whether it is heart attack, stroke or cancer which are the major killers… and ranking up there is also death from infections. Usually viral or bacterial infections can be fatal to many of the elderly because their immune systems are weak. So recently there has been discussion about what if people eating a very healthy calorie restricted diet do not die of the common killers, what would be likely to deliver that final blow. Many conclude, infection related death. Based on some of the evidence in animal models where infections such as influenza and bacterial infections are given to mice and looking at survival between ad libitum and calorie restricted groups, it seems that moderate to severe calorie restriction might increase the risk of death. It seems that in the CR group they do not have enough reserves before to keep them above a critically low weight to sustain life before their adaptive immune system has a chance to take control of the infection. Usually during the time symptoms come on there is a marked decrease in appetite and the bodies resources go into fighting the infection. Fever, increasing metabolic rate, you expend more energy. As you can see below there is a decrease in body weight amongst the both groups but the control animals maintain enough of their body weight to stay alive, whereas the CR group there is a downward trend and the mortality rate reaches 100%
“Weight loss occurs in mice with influenza infection due to a decrease in energy intake and an increase in energy demands. Young and aged mice can lose up to 35% of their body weight and recover from infection, which suggests a critical weight indicative of sufficient energy reserves to recover from infection. Lifelong ER results in a 30% decrease in starting weight that may be only marginally above this critical threshold. In the case of aged ER mice, 100% mortality was observed by d 7 (X), before an adaptive T cell response, suggesting a primary influence of underweight on innate immunity. Adapted from”.
In humans the critical body weight in which there is a critical threat to life is a BMI of 13 in males and 11 in Females. In the study by Dr Luigi Fontana at Washing University in St Louis he has shown that the average BMI for people practicing long term calorie restriction is 19.6 which is above the recommended normal bmi between 18.5-25. This might give more than enough reverses to survive an infection if such a weight is maintained. However, under more severe CR low body weights among humans have been reported as low as a BMI of 15, which could pose a risk to premature death if a severe infection were to occur. Antibiotics would be a very useful in helping ensure that CR does work in humans and is not prevented by excess mortality due to infectious disease. If CR does retard the aging process in humans but the risk of death from infectious remains higher, then this might negate any potential lifespan extension that could be gained from lifelong calorie restriction. During previous times before antibiotics, periods of semi starvation that would have extended the lives of those lived under such conditions if there were better hygiene and treatments for common bacterial infections that are usually easily treated today. Although antibiotics are currently becoming less effective because of the overuse and misuse of antibiotics, newer generations of antibiotics are expected to become available within the next 10 years. Recently, there have been calls for 10 new antibiotics by 2020, and these are to be completely new classes of antibiotics which will work in more novel ways than how the current antibiotics work.
Calorie Restriction improved immunity, theoretically and anecdotally… but what is the actual evidence?
In contrast to the animal evidence which suggests that CR might predispose humans to infections, there is little human evidence to back this up. So far the work on CR effect on immunity in humans hasn’t been looked at. Recently there was a study that showed those who have done short term calorie restriction have improved T cell function, which is crucial against viral infections. Actually this is in-line with the animal evidence also. Also in Rhesus monkeys which are closer to humans biologically and genetically, also have reported to have slowed aging of their immune systems. However, unfortunately the human study was actually not the level of calorie restriction that is used in animal experiments or in the study by DR Fontana at WUSTL. These subjects were overweight, and normalizing their weight by decreasing their calories by 30%, improved immunity. This is not a big surprise. Excess weight puts the body into a state of chronic low grade inflammation, the immune system is chronically activated leading to immune system dysfunction other problems such as asthma, allergies, and autoimmune diseases.
Anecdotal reports from those that are practicing calorie restriction seem to be reporting less infections or absence of infections since starting calorie restriction. However this might not be purely because of the calorie restriction itself, but might be an effect of the foods that are consumed. Plant foods typically contain many compounds that have found to be beneficial in killing bacteria, viruses and fungi. Flavanoids, polyphenols, catechins from green tea, lactoferrin, fatty acids like omega 3, beta glucans which are all generally consumed in far greater amounts in a typical calorie restriction diet. The combination of these compounds might have a synergistic effect in not only attenuating the decrease in immune systems capability to deal with the infection, but also directly inhibit infections. I will look at a few compounds that have shown to be promising in fighting infections.
Beta glucans – Beta glucans are derived from yeast and also oats. Oat beta glucans is mildly effective at increasing immunity, as shown in one study where they showed that in humans, oat beta glucan was able to offset the negative effects of exercise stress .
“Exercise stress was associated with a 28% increase in morbidity (P = 0.036) and 18% increase in mortality (P = 0.15). Ingestion of ObetaG before infection prevented this increase in morbidity (P = 0.048) and mortality (P = 0.05)”
The immune system modulating effects of beta glucans has been known for a couple of decades. When you ingest the beta glucan from yeast the glucan molecules are unaffected by the acid of your stomach and pass through unchanged, once they are absorbed into the blood they are taken up my phagocytes which digest them, and then over a period of days slowly release the glucan molecules and they attach to beta glucan receptors on the cell surface of macrophages. This causes a cascade of effects which basically makes the immune system on alert, ready to attack any foreign invaders. Increased NK cytotoxicity, an increase in the number of macrophages which basically eat bacteria and dead cells and digest them within the lysosomes. Beta glucans increase a number of cytokines which attract immune cells to the site of infection, but without increasing IL-1 which is responsible for pyrexia.
One particular blend of alpha and beta glucans has a powerful effect on the immmune system
* Increasing the production of cytokines
* Increasing the activity of NK cells by as much as 300-800%
* Increasing populations of macrophages, in some cases doubling them
* Increasing the number of dendritic cells
* Increasing the number of T cells by as much as 200%
I believe that a beta glucan supplement, even if periodically taken during times where infection risk is higher at times of influenza outbreaks, norovirus outbreaks etc… Then it can be taken at these times since the effect on immunity is quite rapid.
Direct inhibitors or of pathogens
Tea polyphenols – Catechins that are found in green tea and white tea have anti viral, anti bacterial and anti fungal properties, EGCG is able to work in many different ways. Again viruses it not only alters the protein coating around the virus, but also blocks neuraminidase activity so that the virus is not able to be released from the host’s cell. A popular drug named drug oseltamivir which was widely used in the recent swine flu breakout also uses the same target to reduce symptoms of viral infections. One study in a Japanese care home they reported that influenza was reduced by over 90% if green tea was gargled every day. But the sample size was small. Green tea is a very safe beverage and with plenty of other benefits even if it doesn’t offer complete protection against influenza infections. Which are a big cause morbidity and death in the elderly. Secondary bacterial infections, lung infections primarily are the cause of death. EGCG can kill many times of bacteria, inhibit biofilm formation, and also enhance the effects of antibiotics so that they that they work better. In some cases reverse antibiotic resistance. Green tea also actually boosts the immune system.
“Among subjects taking CSF there were 32.1% fewer subjects with symptoms (P = 0.035), 22.9% fewer overall illnesses of at least 2 days duration (P = 0.092), and 35.6% fewer symptom days (P < p =” 0.017)” p =” 0.046)” style=”font-weight: bold;”>Vitamin D –
Vitamin D – This is one has had a lot of attention recently in the media. Researchers are beginning to understand its effects on immunity, and how it’s an immune system modulator. In that it basically makes the immune system smarter so that it can identify foreign pathogens and the innate immune system deals with it before it can take hold. Vitamin D3 when above a certain level in the blood is stored. Recent reports show that patients that take vitamin D3 report less colds and flu and it’s believed because vitamin D3 is a powerful inducer of LL37 peptides that punch holes in viruses, bacteria and fungi . It’s recommended that optimal levels of 25 (OH) D are above 32ng. 1000IU of vitamin D3 tends to raise blood levels but approx 10ng.
Lactoferrin – Lactoferrin protects the body by binding to iron so that that the bacteria cannot use it. In breast milk there is a lot of lactoferrin and this is one of the reasons why babies who are breast fed have better immune systems. Lactoferrin coats anywhere where germs can gain entry into the body. Such as, the nose, eyes, sex organs. Consuming lactoferrin supplements is thought to be beneficial in protecting against infections. Lactoferrin is part of the innate immune system and is one of the first barriers to infection.
Ginger – It is a well known anti emetic. Meaning, it prevents sickness and nausea. Some doctors instruct women to use it while pregnant and have got morning sickness; other uses are travel sickness, general nausea and indigestion, acid reflux disease. The only one it doesn’t seem to be effective for is when use post operatively (after operation with G.A). It can be also used to help unblock the noise and is a weak antiviral so could help with cold symptoms.
D Mannose – 90% of UTI infections are caused by E coli bacteria. Usually D mannose is completely effective at being able to remove E coli from the bladder. Along the bladder surface there are D mannose receptors which the E coli bacteria attach to. When you consume D mannose (which is found in small amounts in cranberry juice, also known for its ability to prevent infections by making the bladder wall slippery so that bacteria cannot attach) the D mannose is not absorbed by the body and majority of it ends up in the urine. Once you flush out your bladder the E coli detaches from the bladder wall and has a higher affinity for the D mannose within the urine. The best thing about this cure is that there is no chance for resistance and it will clear any antibiotic resistant bacteria. Unfortunately for those unlucky 10% of infections, D mannose might not work and antibiotics are usually required. I highly recommend D mannose, especially for women as they are much more prone to infections than men. Please read this site; http://www.d-mannoseworks.com/ D mannose is a lot more effective than cranberry juice.
Manuka Honey – at least 10UMF, which is the strength of the honey, is able to kill even the most resistant pathogens against antibiotics. In fact, the university hospital in Cardiff, Wales, have been testing on wounds . Not only is it a great anti inflammatory but it also helps kills MRSA infections, and other pathogens. Consuming Manuka honey is good for the throat and could prevent any throat infections like strept throat, and it could also prevent stomach infections like H pylori and food poison.
Garlic – It has been known for a very long time that garlic was a good anti bacterial, and anti viral. The compound responsible for this is the one that gives off that funny smell when you eat too much… but wouldn’t you rather just smell a bit of garlic than be sick? I know I would. There was a report a few years back saying that ‘garlic is the common cold cure’. Well not quite, however it does seem to do a remarkable job at reducing the number of colds, and reducing the number of days being ill. From BBC news website that reported on the garlic study
“Over a 90-day period during the winter when most colds occur, just 24 colds were recorded among those taking the supplement, compared to 65 amongst those taking the placebo. The study also found that those taking the supplement that did catch a cold were more likely to make a speedier recovery than those taking the placebo and the chances of re-infection following a cold were significantly reduced”
Probiotics – Antibiotics that are taken so often destroy both good and bad bacteria. I recommend consuming probiotic yogurts or to get a probiotic supplement. This will improve immunity, calm the immune system to help allergies, and also protect from overgrowth of organisms that can can disease.
If there was one supplement that I would take to increase resistance against pathogens it would be Beta glucans, specifically AHCC because of the science behind it is quite strong. Please do read the references below for more detailed information on this compound, and visit the website http://www.ahccresearch.com/how-ahcc-works.html to look at other studies listed and how the ahcc works
The combination of a good diet, calorie restriction, the knowledge of medicinal foods and modern medicine, I believe it’s possible to live a very long time. Be well. Free of disease, and live a long healthy life.
 Barry W. Ritz and Elizabeth M. Gardner. Malnutrition and Energy Restriction Differentially Affect Viral Immunity http://jn.nutrition.org/cgi/content/full/136/5/1141
 Davis JM, Murphy EA, Brown AS, Carmichael MD, Ghaffar A, Mayer EP. Effects of oat beta-glucan on innate immunity and infection after exercise stress. http://www.ncbi.nlm.nih.gov/pubmed/15292739
 Messaoudi, J. Warner, M. Fischer, B. Park, B. Hill, J. Mattison, M. A. Lane, G. S. Roth, D. K. Ingram, L. J. Picker, D. C. Douek, M. Mori, and J. Nikolich-Zugich. Delay of T cell senescence by caloric restriction in aged long-lived nonhuman primates. Proc Natl Acad Sci U S A 103 (51):19448-19453, 2006.
 Ahmed T, Das SK, Golden JK, Saltzman E, Roberts SB, Meydani SN. Calorie restriction enhances T-cell-mediated immune response in adult overweight men and women. J Gerontol A Biol Sci Med Sci. 2009 Nov;64(11):1107-13. Epub 2009 Jul 28.
 Synergistic effect of nonspecific immunostimulation and antibiotics in experimental peritonitis. http://www.ncbi.nlm.nih.gov/pubmed/3303398[
Supplementation with active hexose correlated compound increases survival following infectious challenge in mice. http://www.ncbi.nlm.nih.gov/pubmed/18752476?
 Active hexose correlated compound (AHCC) enhances resistance to infection in a mouse model of surgical wound infection. http://www.ncbi.nlm.nih.gov/pubmed/17233570
 Prophylactic efficacy of a basidiomycetes preparation AHCC against lethal opportunistic infections in mice http://www.ncbi.nlm.nih.gov/pubmed/10946621
 Antiviral Res. 2005 Nov;68(2):66-74. Epub 2005 Aug 9 Antiviral effect of catechins in green tea on influenza virus http://www.ncbi.nlm.nih.gov/pubmed/16137775
 Rowe CA, Nantz MP, Bukowski JF, Percival SS.
Specific formulation of Camellia sinensis prevents cold and flu symptoms and enhances gamma,delta T cell function: a randomized, double-blind, placebo-controlled study. http://www.ncbi.nlm.nih.gov/pubmed/17914132
 Ziv OREN, Jeffrey C. LERMAN*, Gudmundur H. GUDMUNDSSON†, Birgitta AGERBERTH‡ and Yechiel SHAI Structure and organization of the human antimicrobial peptide LL-37 in phospholipid membranes: relevance to the molecular basis for its non-cell-selective activity http://www.biochemj.org/bj/341/0501/bj3410501.htm
 Is honey the answer to the MRSA crisis http://www.walesonline.co.uk/news/health-news/tm_objectid=16320886&method=full&siteid=50082&page=1&headline=is-honey-the-answer-to-the-mrsa-crisis–name_page.html