Tampilkan postingan dengan label immune system. Tampilkan semua postingan
Tampilkan postingan dengan label immune system. Tampilkan semua postingan

Sabtu, 18 Juni 2016

The 'Wim Hof Method' - Effective? What Science Can Tell Us

If someone markets his program the way Hof does, i.e. as a means to "Become A 'Super' Version Of Yourself In Just 10 Short, Life Transforming Weeks" (WimHofMethod.com), you should rightly be skeptical.
You know that I am no fan of "works for me (N=1), so buy my e-book"-approaches. Until recently, the so-called "Wim Hof Method" was yet exactly that: an N=1 (+ dubious X) approach to health and performance enhancement... and yes, that is "until recently", or rather "until two years ago", because two years ago, Matthijs Kox and colleagues from the Nijmegen Institute for Infection, Inflammation and Immunity, the Radboud University (will wonders never cease) the Yale University School of Medicine (Kox. 2014) published a study with the not so telling title "Voluntary activation of the sympathetic nervous system and attenuation of the innate immune response in humans" in the peer-reviewed scientific journal PNAS.

The study used a parallel randomized controlled design and was registered at ClinicalTrials.gov as NCT01835457. After approval by the local ethics committee of the Radboud University Nijmegen Medical Centre (CMO 2012/455), 30 healthy, nonsmoking, Dutch male volunteers were included in the trial.
Hof's method should advice to eat cholesterol-laden immune-boosting foods like meats

You May Eat Pork, too!

You Eat What You Feed!

Meat & Prostate Cancer?

Meat - Is cooking the problem

Meat Packaging = Problem?

Cholesterol for Your Immunity
Exclusion criteria were: febrile illness during the 2 wk before the endotoxemia experiment, taking any prescription medication, history of spontaneous vagal collapse, practicing or experience with any kind of meditation, or participation in a previous trial where LPS was administered.
Table 1: Subject demographic characteristics (Kox. 2014).
The subjects were randomly allocated to the trained group (n = 18) or the control group (n = 12) by the opening of a sealed envelope prepared by a research nurse not involved in the study. After having fulfilled the training program, 12 of the 18 trained subjects were randomly assigned to participate in the experimental endotoxemia experiments (see Figure 1).

The study itself (which excluded several of the originally 30 subjects, because their reaction to endotoxemia, i.e. the influx of  (potentially) pathogenic metabolic byproducts of bacteria into their blood was "odd" (i.e. too extreme as in too low or too high) was sequentially conducted in two identical blocks, each consisting of nine subjects in the trained group (of which six finally participated in the endotoxemia experiments) and six subjects in the control group. As the authors point out,
"[...t]his design was chosen to minimize the bias due to differences in the interval between the end of the training period and the endotoxemia experiments. As the aim of [their] study was to investigate the effects of the training intervention on the innate immune response in a standardized model of systemic inflammation, [they] did not assess the effects of the training intervention on immune system parameters in the absence of endotoxemia" (Kox. 2014). 
A schematic overview of the study design (one block) is depicted in Fig. S3. The trained group was trained by Dutch individual Wim Hof and three trainers who previously received an instructor course by Wim Hof to become a trainer. A medical doctor of the study team (L.T.v.E.) and the principal investigator (M.K.) were present during all training sessions (in Poland and in The Netherlands), and during the experimental endotoxemia experiments. The first 4 d of the training program took place in Poland and were most intensive.
The Internet is full of praise for Hof's method, but that's not scientific eviden-ce (infographic from therenegade-pharmacist.com)... it does show that Hof is a good marketer, though ;-)
What did the program look like? The program consisted of three main elements: meditation, exposure to cold, and breathing techniques. (i) Meditation: so-called “third eye meditation,” a form of meditation including visualizations aimed at total relaxation. (ii) Voluntary cold expo-sure: standing in the snow barefoot for up to 30 min and lying bare chested in the snow for 20 min; daily dipping / swimming in ice-cold water (0–1 °C) for up to several minutes (including complete submersions); and hiking up a snowy mountain (elevation: 1,590 m) bare chested, wearing nothing but shorts and shoes at temperatures ranging from −5 to −12 °C (wind chill: −12 to −27 °C).

(iii) Breathing techniques,
consisting of two exercises: in the first exercise subjects were asked to hyperventilate for an average of 30 breaths. Subsequently, the subjects exhaled and held their breath for ∼2–3 min (“retention phase”). The duration of breath retention was entirely at the discretion of the subject himself. Breath retention was followed by a deep inhalation breath, that was held for 10 s. Subsequently a new cycle of hyper/hypoventilation began. The second exercise consisted of deep inhalations and exhalations in which every inhalation and exhalation was followed by breath holding for 10 s, during which the subject tightened all his body muscles. These two breathing exercises were also performed during the endotoxemia experiments. Additional element of the training program consisted of strength exercises (e.g., push-ups and yoga balance techniques).
After returning from Poland, the subjects practiced the techniques they learned daily by themselves at home (2–3 h/d; cold exposure was achieved through taking cold showers) until the endotoxemia experiment day (5–9 d later).
Figure 1: Study design. This block was carried out twice in identical fashion, resulting in 12 subjects in both groups that underwent experimental endotoxemia. CT, control subject; TR, trained subject (Kox. 2014).
After training the method at home, all subjects returned to the lab, where a final group training took place and at the end of this day, six of the nine trained subjects (in each block) were randomly selected for participation in the endotoxemia experiments, using the sealed envelope method. Then, ...
"[...t]he selected subjects practiced in a final training session led by Wim Hof on the day before the endotoxemia experiment day. Wim Hof was present to coach the subjects during the endotoxemia experiment days during the 3 h that the subjects in the trained group practiced the learned techniques. The control group did not undergo any training procedures throughout the study period" (Kox. 2014).
To evaluate the effect of Hof's method on the subjects' immune system, the subjects, who had refrained from caffeine- or alcohol-containing substances 24 h before the start of the experiment, and food 10 h before the start of the endotoxemia experiment, were injected purified lipopolysaccharides from Escherichia coli, which were supplied as a lyophilized powder that was reconstituted in 5 mL saline 0.9% for injection and vortex mixed for at least 20 min after reconstitution.
Figure 2: Cardiorespiratory parameters, temperature, and symptoms (A-I), as well as plasma
cathecholamine concentrations and serum cortisol concentrations during experimental endotoxemia
in control (dotted line) and trained (solid line) subjects (J-M | Kox. 2014).
As the scientists point out, "[t]he LPS solution was administered as an i.v. bolus injection at a dose of 2 ng/kg body weight in 1 min at T = 0 h (Kox. 2014). More specifically, ...
"[...a] cannula was placed in an antecubital vein to permit infusion of 0.9% NaCl solution; the subjects received 1.5 L 0.9% NaCl during 1 h starting 1 h before endotoxin infusion (prehydration) as part of our standard endotoxemia protocol (29), followed by 150 mL/h until 6 h after endotoxin infusion and 75 mL/h until the end of the experiment" (Kox. 2016).
To estimate the effect of the breathing techniques, the authors measured not just cardiorespiratory parameters, temperature, and symptoms, but also the levels of catecholamines, cortisol and plasma cytokines (stress), as well as the leukocyte count (immune reaction) and conducted correlation analyses of all these variables.
Figure 3: Plasma cytokine concentrations during endotoxemia in control and trained subjects. (A, C, E, and G) Median values of pro- (TNF-α, IL-6, and IL-8) and anti-inflammatory (IL-10) cytokines (n = 12 per group). (B, D, F, and H) Median ± interquartile range of area under curve (AUC) of pro- (TNF-α, IL-6, and IL-8) and anti-inflammatory (IL-10) cytokines (n = 12 per group; unit: ×104 pg/mL·h). P values were calculated using Mann–Whitney u tests (Kox. 2014).
The results are - initially (eventually, it's a normal stress response, see Bottom Line)- quite astonishing, as the "intervention group, practicing the learned techniques" (Kox. 2014) didn't just show symptoms of being suffocated, i.e. am intermittent respiratory alkalosis and hypoxia resulting and corresponding increases in the levels of the stress hormones epinephrine in the blood, but also ...
  • Figure 3: Correlation analysis (Kox. 2014).
    significant increases of the anti-inflammatory cytokine IL-10, which correlated strongly with the preceding increase in epinephrine levels (see Figure 3A), as well as
  • significant reductions of the proinflammatory mediators TNF-α, IL-6, and IL-8, which, in turn, correlated negatively with IL-10 levels.
In conjunction with the significant reduction of "flu-like symptoms", the scientists observed in the intervention group, the study at had does therefore in fact "demonstrate that voluntary activation of the sympathetic nervous system results in epinephrine release and subsequent suppression of the innate immune response in humans in vivo" (Kox. 2015).
Wow! This really works!? Yes, the study at hand confirms that the long-held theory that both, the autonomic nervous system and innate immune system, cannot be voluntarily influenced must be considered disproven - the "Wim Hof Method", of which the authors of the present paper highlight that it consists of techniques that can be "learned in a short-term training program" (Kox. 2014) seems to do what scientists have long considered impossible: it allows people like you and me to directly influence their sympathetic nervous system and immune system in a way that triggers highly pronounced increases in the stress hormone epinephrine and down-stream immune effects in form of increases of the production of anti-inflammatory mediators and a subsequent dampening of the proinflammatory cytokine response to an (albeit artificial) immune challenge with bacterial endotoxin.

Believe it or not, but an intense workout will have pretty much the same effects on inflammation (in this case triggered by the workout itself) as the "unique" Hof Method (figure from Petersen. 2005; expanded). A study that evaluates the conditioning effect in the same endotoxin model has yet, as far as I know, still to be done.
As Kox et al. point out, their study "could have important implications for the treatment of a variety of conditions associated with excessive or persistent inflammation, especially autoimmune diseases in which therapies that antagonize proinflammatory cytokines have shown great benefit" (Kox. 2014). Before these benefits have scientifically proven, though, I would like to remind you that exercise can induce similar increases in epinephrine, subsequent increases in IL10 and corresponding decreases of various inflammatory cytokines (Brandt. 2010, Petersen. 2005 & 2006; just as simply injecting or increasing epinephrine by other means will | Van Der Poll. 1997), albeit in response to exercise alone, not in response to endotoxin exposure. Whether the response to this stressor would be similarly conditioned and would thus affect endotoxin assaults, has imho not been investigated | Comment!
References:
  • Brandt, Claus, and Bente K. Pedersen. "The role of exercise-induced myokines in muscle homeostasis and the defense against chronic diseases." BioMed Research International 2010 (2010).
  • Kox, Matthijs, et al. "Voluntary activation of the sympathetic nervous system and attenuation of the innate immune response in humans." Proceedings of the National Academy of Sciences 111.20 (2014): 7379-7384.
  • Pedersen, Bente Klarlund, and Laurie Hoffman-Goetz. "Exercise and the immune system: regulation, integration, and adaptation." Physiological reviews 80.3 (2000): 1055-1081.
  • Petersen, Anne Marie W., and Bente Klarlund Pedersen. "The anti-inflammatory effect of exercise." Journal of applied physiology 98.4 (2005): 1154-1162.
  • Petersen, A., and B. Pedersen. "The role of IL-6 in mediating the anti inflammatory." J Physiol Pharmacol 57 (2006): 43-51.
  • Van Der Poll, Tom, and Stephen F. Lowry. "Epinephrine inhibits endotoxin-induced IL-1β production: roles of tumor necrosis factor-α and IL-10." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 273.6 (1997): R1885-R1890.

Sabtu, 30 April 2016

Cholesterol Boosts Your Immune Defenses: Infections Can Lower Cholesterol, Extra-Chol. Will Help You Battle Them

Health food for sick people - Much better than cholesterol supplements ;-)
Cholesterol is the villain of the 20th century. In the 21st century, however, the evidence that vilifying the building-block of hormones and cell membranes has more negative than positive consequences is accumulating.

The latest piece to the pro-cholesterol puzzle is a study from the Capital Medical University (Wang. 2016) in Beijing, China. A study in which the researchers tried to get to the bottom of the proven link between cholesterol and several adverse outcomes in various disesase - especially infectious ones.
Meat is an excellent source of cholesterol, too | Learn more about meat at the SuppVersity

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The authors conducted a study to supplement cholesterol, and observe the change on the test indexes and the severity of disease. Their randomized and controlled clinical trial was conducted at the infectious disease department in Beijing Friendship Hospital, Capital Medical University, Beijing, between January 2011 and December 2012.

The subjects were hospitalized patients with pulmonary infection, patients who were assigned into intervention group and control group randomly and subsequently received a 10-day course of either
  • extra 600mg cholesterol per day (provided by the egg yolk) or 
  • a placebo supplement devoid of cholesterol, but w/ the equivalent amount of vitamin A
to see how the extra cholesterol would affect the course of the subjects' illnesses. In that, the extra-vitamin-A in the control group is crucial, because of retinols paramount importance in the immune response to infections (Glasziou. 1993; Semba. 1994 | see Figure 1):
Figure 1: Effects of vitamin A on the mortality outcomes of various illnesses (Glasziou. 1993).
In conjunction with the dietary standardization, which involved a protein intake standard of 1.0g/kg ideal body weight (50% high quality protein), a carbohydrate intake standard of 50-60% of the total energy intake (mostly complex carbohydrates) and a fa

t intake of below 30% of the predetermined optimal energy intake for each of the patients, the scientists tried to ensure that no external factors would interfere with the recovery of their hospitalized (=tightly controlled) patients.
Figure 2: Effects of treatment / placebo on total cholesterol and SAPSII scores (Wang. 2016).
And guess what? The scientists' statistical analysis of the differences on indexes between after 10-day intervention in intervention group and after 10-day observation in control group showd significant differences in seven indexes, total cholesterol (TC), Body Mass Index (BMI), albumine (ALB), pre-albumin (PA), CRP, IL-6 and, most importantly, the severity of disease.
"Eggs" - 4-Letter Food Improves Both Cholesterol Particle & Phospholipid Profile + HDL's Effects | more
"The increased concentrations of TC, ALB and PA in intervention group were more than those changes in control group. The BMI in intervention group was increased more than that in control group.

The decreased concentrations of CRP and IL-6 in intervention group were more than those changes in control group. The improvement of severity of disease in intervention group was more obvious than that in control group. The improvement of nutrition status in intervention group was significant" (Wang. 2016).
Now, you can argue that all that may be due to other ingredients in the egg-yolk, but let's be honest: if infections, especially pneumonia and pulmonary infection disease, can lead to hypocholesterolemia and supplementation of cholesterol properly can improve the nutritional status, decrease the severity of disease, and improve the prognosis of disease, that's quite a convincing piece of evidence in favor of the importance of cholesterol in our bodies' fight against infections.
Bottom line: Yes, you can argue that cholesterol is a "vitamin" in infectious disease - a vitamin in the sense of a nutrient of which your body cannot produce enough on its own as a consequence of infections like pneumonia and pulmonary infection disease.

The yolk is where almost all the "good" stuff in the eggs resides. Throwing the yolk of the 1-2 eggs you eat per day away, as people have been doing it for decades is thus madness | more
I suspect that you will still share my doubts that increasing a patient's cholesterol will in fact become the "new therapeutic target" in the treatment of infection diseases - and that in spite of the fact that this kind of "treatment" could, as the authors point out, be of particular importance in the elderly, where, in clinical practice, doctors obviously "have not fully realized the impact of low cholesterol level" (Wang. 2016). Rather than to "consider [... a] cholesterol treatment for [their] patients" (ibid.), doctors will continue to administer statins and enteral nutrition solutions that are devoid of the amounts of cholesterol of which the study at hand shows that they are critical to support patients' (and probably athletes) immune systems | Comment!
 References:
  • Glasziou, P. P., and D. E. Mackerras. "Vitamin A supplementation in infectious diseases: a meta-analysis." Bmj 306.6874 (1993): 366-370.
  • Semba, Richard D. "Vitamin A, immunity, and infection." Clinical Infectious Diseases 19.3 (1994): 489-499.
  • Wang, Jia, and Zhong-xin Hong. "Cholesterol Supplement can Alleviate the Severity of Pulmonary Infection of Patients with Hypocholesterolemia." Journal of Food and Nutrition Research 4.3 (2016): 131-136.

Minggu, 24 Januari 2016

Elimination Diet Kickstarts Fatloss in "People Who Cannot Lose Weight" - 16% Body Fat Reduction in 6 Months, But...

Many of these foods contain supposed allergens and have thus to be eliminated from your diet... is it any wonder that this triggers weight loss? Hardly...
While I have to admit that I am a bit skeptical about the reliability of the results of a recent study from the Sifa University, Faculty of Health Sciences in Turkey, I cannot ignore that Meltem Yaman Onmus, Elif Cakirca Avcu, and Ali Saklamaz claim that "people who cannot lose weight by low-calorie diet can lose weight and fat with elimination diet according to the results of FI [food intolerance] test. FIED [FI elimination diet] is also significantly effective in triglyceride levels" (Onmus. 2016). I know that sounds as if it was taken from the latest unreferenced blogpost on a dubious website, but let's not judge prematurely and instead take a closer look at the design and results of the study.
Unlike elimination diets, fasting must be considered a scientifically proven weight loss trick

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Breakfast? (Un?) Biased Review
82 patients (24 male, 58 female) were included in the study. The mean age was 42.04±11.81 (18-65 years). All of them were "unable to lose weight", i.e. patients who said of themselves that they couldn’t lose weight by diet programs and who had a positive reaction to at least one nutrient in food intolerance test and a BMI value ≥ 25kg/m² - in other words: the subjects were the average Internet bullet-in board dwellers searching for the "magic key" to weight loss.

This is obviously an important fact, because it increases the significance of the study for said group of subjects. Whether the results are significant for anyone else, though, is questionable, since patients who had no food reaction in food intolerance test were excluded from the study. The same goes for subjects who had chronic diseases like diabetes mellitus, coronary heart disease, renal diseases, etc., or individuals who use(d) weight loss drugs and who had allergy to any drug or food and who overuse medications or have pure menstrual migraine or headache that associated a disorder.
No health benefits from "eliminating" foods: Interestingly, the food intolerance elimination diet failed to do what its proponents say it's actually doing: Improve the subjects health. With the exception of a statistically significant decrease in triglyceride levels, there was no improvement in health markers (fasting blood glucose, A1C, total cholesterol, HDL-cholesterol, LDL-cholesterol, AST, and ALT) the scientists didn't observe in the control group, too.
As you can see in Figure 1, this particular group of subjects saw significant benefits from following a diet that did not allow the subjects to consume any of the foods to which they showed an IgG response in the previously conducted food intolerance test for 6 months. Otherwise, the diets of the elimination diet (ED) and control diet were personalized diets with "identical" (according to the size, weight, physical activity, dietary habits and socioeconomic status) energy content.
Figure 1: Pre- and post-intervention weight, body fat, lean body mass, and waist / hip ratio (x10); * indicates significant inter-group difference, this means that everything, but the effect on lean mass was sign. more pronounced in the ED group.
Against that background it is unquestionably striking that the subjects in the elimination diet group lost 16% body fat, while the control group didn't lose either significant amounts of fat or weight. Now, the obvious question is: "Which foods were eliminated?" Unfortunately, this question is neither answered in the study at hand, nor in previous studies showing that elimination diets reduce also reflux disease, chronic fatigue syndrome, and headaches (Selvin. 2007; Akmal. 2009).
Unlike Onmus et al., Akmal et al. publish-ed a list of allergens their IgG test could supposedly identify. A list eliminated foods is yet missing from study, too.
Why's it a problem that we don't know which foods were eliminated? Actually, the answer to this question should be obvious. Let's assume you're "allergic" to sugar, alcohol and high omega-6 vegetable oils like soybean oil. Would you be surprised if you lost significant amounts of body fat if you dropped all sugary and pro-inflammatory high omega-6 foods and stopped drinking alcohol? I, for my part, wouldn't and I guess you wouldn't and you certainly shouldn't be surprised either.

Accordingly, the study at hand does unfortunately not provide enough information to decide whether it provides convincing evidence of using IgG-tests to guide you when you're designing diets for yourself or your clients. Hopefully future research will do just that | Comment!
References:
  • Akmal, Mohammed, Saeed Ahmed Khan, and Abdul Qayyum Khan. "The Effect of the ALCAT Test diet therapy for food sensitivity in patient’s with obesity." Middle East Journal of Family Medicine 7.3 (2009).
  • Onmus, Meltem Yaman, Elif Cakirca Avcu, and Ali Saklamaz. "The Effect of Elimination Diet on Weight and Metabolic Parameters of Overweight or Obese Patients Who Have Food Intolerance." Journal of Food and Nutrition Research 4.1 (2016): 1-5.
  • Selvin, E., Paynter, N. P., Earlinger T. P. "Nutrition and allergy." Arch Intern Med, 167.1 (2007): 31-39.