Dairy reduces inflammation and oxidative stress in metabolic syndrome

Posted on September 3, 2011 by Dr. Jonathan

More evidence that dairy foods contain agents with antiinflammatory and antioxidant properties is presented in a study published recently in The American Journal of Clinical Nutrition showing reductions in damaging inflammatory biomarkers. The authors state:

“Oxidative and inflammatory stress are elevated in obesity and are further augmented in metabolic syndrome. We showed previously that dairy components suppress the adipocyte- and macrophage-mediated generation of reactive oxygen species and inflammatory cytokines and systemic oxidative and inflammatory biomarkers in obesity…The objective of this study was to determine the early (7 d) and sustained (4 and 12 wk) effects of adequate-dairy (AD) compared with low-dairy (LD) diets in subjects with metabolic syndrome.”

Their forty overweight or obese subjects with metabolic syndrome were randomly assigned to receive either an ‘adequate dairy diet’ (defined as 3.5 daily servings) or ‘low dairy diet’ (less than half a daily serving) form of weight-maintenance diet for 12 weeks. They measured oxidative and inflammatory biomarkers at the start and after 1, 4, and 12 weeks as primary outcomes, along with body weight and composition to start and after 4, and 12 weeks as secondary outcomes. Their data showed a dramatic difference for the ‘adequate dairy’ diet:

“AD decreased malondialdehyde and oxidized LDL at 7 d (35% and 11%, respectively), with further decreases by 12 wk. Inflammatory markers were suppressed with intake of AD, with decreases in tumor necrosis factor-α at 7 d and further reductions through 12 wk (35%); decreases in interleukin-6 (21%) and monocyte chemoattractant protein 1 (14% decrease at 4 wk, 24% decrease at 12 wk); and a corresponding 55% increase in adiponectin at 12 wk. LD exerted no effect on oxidative or inflammatory markers. Diet had no effect on body weight; however, AD significantly reduced waist circumference and trunk fat, and LD exerted no effect.”

While these findings don’t obviate the need to attend to the possibility of dairy allergies or the quality of dairy foods consumed, this is strong evidence that there agents in an ‘adequate dairy’ diet that can do more than a low dairy diet even when the same amount of weight is lost.

“Data from this study show that an increase in dairy intake from suboptimal to adequate levels (≈3.5 servings/d) significantly attenuates both oxidative and inflammatory stress in metabolic syndrome. Notably, although these effects may result, in part, from reductions in adiposity on higher dairy diets, the rapid onset (within the first 7 d of dietary change) suggest that there is an adiposity-independent effect as well. This is further supported by our previous evidence that showed direct effects of dairy components on adipocyte cytokine expression and secretion.”

Pro-inflammatory cytokines of rheumatoid arthritis reduced by Vitamin B6

Posted on July 11, 2010 by Dr. Jonathan

We’re always on the lookout for physiological agents that have the potential to calm the activity of pro-inflammatory cytokines when they are elevated in autoimmune disease. An exciting finding was reported in a paper just published in the European Journal of Clinical Nutrition:

“The purpose of this study was to investigate whether vitamin B6 supplementation had a beneficial effect on inflammatory and immune responses in patients with rheumatoid arthritis (RA).”

The control group of patients was given 5 mg/day of folic acid only while the study group was given 100 mg/day of vitamin B6 in addition for 12 weeks. Indicators of inflammation (C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and lymphocyte subsets were measured on day 1 (week 0) and after 12 weeks (week 12) of the intervention.

At the end of twelves the data painted this picture:

“In the group receiving vitamin B6, plasma IL-6 and TNF-α levels significantly decreased at week 12. Plasma IL-6 level remained significantly inversely related to plasma PLP (pyridoxal 5′-phosphate, B6) after adjusting for confounders.”

The bottom line conclusion is worth bearing in mind when evaluating any autoimmune disorder because underlying causal factors are similar regardless of the specific tissue under attack:

“A large dose of vitamin B6 supplementation (100 mg/day) suppressed pro-inflammatory cytokines (that is, IL-6 and TNF-α) in patients with RA.”

Just seeing someone who is sick can increase proinflammatory cytokines

Posted on June 12, 2010 by Dr. Jonathan

Those interested in how image and perception modify gene expression and immune function will appreciate this paper recently published in the journal Psychological Science.

“An experiment…tested the hypothesis that the mere visual perception of disease-connoting cues promotes a more aggressive immune response.”

The experimental subjects were exposed to either photographs depicting symptoms of infectious disease or photographs of guns.

“After incubation with a model bacterial stimulus, participants’ white blood cells produced higher levels of the proinflammatory cytokine interleukin-6 (IL-6) in the infectious-disease condition, compared with the control (guns) condition.”

This may not be the first study to demonstrate this effect, but the authors assert…

“These results provide the first empirical evidence that visual perception of other people’s symptoms may cause the immune system to respond more aggressively to infection.”

It’s well known that though we can cognitively discriminate between a photo depicting infection and the immediate material presence of it, our autonomous physiological response does not. Now consider the significance for autoimmune disease when there is hyperarousal of attention to the possibility of infection. This is one of the reasons why I am convinced that dogmatically insisting on a diagnosis of chronic infection (such as Lyme disease) when the most sensitive and advanced tests provide zero evidence—and at the same time demonstrable autoimmune phenomena are present—is doing patients a disservice.

Depression involves brain inflammation

Posted on April 1, 2010 by Dr. Jonathan

Biological Psychiatry Not to oversimplify since depression can have multiple contributing causes, but there have been many studies published about brain inflammation as an important component of major and minor depression. An illuminating paper published in the latest volume of the journal Biological Psychiatry undertakes an extensive analysis of accumulated scientific evidence. The authors begin by noting:

“Major depression occurs in 4.4% to 20% of the general population. Studies suggest that major depression is accompanied by immune dysregulation and activation of the inflammatory response system (IRS). Our objective was to quantitatively summarize the data on concentrations of specific cytokines in patients diagnosed with a major depressive episode and controls.”

Cytokines are, among other things, signalling molecules that regulate immune system function. This has great practical significance because there is an evidence-based approach in functional medicine to analyzing and treating cytokine imbalances. The authors evaluated 24 studies that included eight different cytokines. Here’s what their data showed:

“This meta-analysis reports significantly higher concentrations of the proinflammatory cytokines TNF-α and IL-6 in depressed subjects compared with control subjects…this meta-analytic result strengthens evidence that depression is accompanied by activation of the IRS.”

You may enjoy the interesting comment on this study just published in Journal Watch.

Although this is a valuable study it’s important to keep a broad perspective. Here’s another paper published not long ago in the journal Pharmacopsychiatry, one among many others on cytokines and depression. It documents cases of brain inflammation with a different cytokine pattern. This paper is also interesting for the therapeutic comparison of Prozac and electroacupuncture:

“An increase in inflammatory response and an imbalance between T-helper (Th) 1 and 2 functions have been implicated in major depression. The aims of the present study were to 1) study the relationship between pro- and anti-inflammatory cytokines and between Th1 and Th2 produced cytokines in depressed patients and 2) evaluate and compare the effect of treatments with electroacupuncture (EA) and fluoxetine on these cytokines.”

Th1 and Th2 are the two primary poles of immune system function, cell-mediated and humoral (antibody). Imbalances result in immune dysregulation. Fluoxetine is Prozac. (The inclusion of electroacupuncture might tip you off that this study was done in Germany.) Their data tells a fascinating story:

“Increased proinflammatory cytokine interleukin (IL)-1β and decreased anti-inflammatory cytokine IL-10 were found in the depressed patients. By contrast, Th1 produced proinflammatory cytokines, tumor necrosis factor (TNF)-α and interferon (IFN)-γ were decreased, and Th2 produced cytokine IL-4 was significantly increased in depressed patients…Both acupuncture and fluoxetine treatments, but not the placebo, reduced IL-1β concentrations in responders. However, only acupuncture attenuated TNF-α concentration and INF-γ/IL-4 ratio towards the control level.”

How interesting that what we call a peripheral sensory nervous system modality (stimulation of the brain through the peripheral sensory nerves, in this case with electroacupuncture) reduced inflammation and TNF-α. This corresponds exactly with my clinical experience employing these modalities for a range of conditions including autoimmune disorders, and explains part of why patients feel so much better after a treatment. Their conclusion is worth noting:

“These results suggest that an imbalance between the pro- and anti-inflammatory cytokines (IL-1 and IL-10), and between Th1 and Th2 cytokines (INF-γ or TNF-α and IL-4) occurred in untreated depressed patients. Both EA and fluoxetine had an anti-inflammatory effect by reducing IL-1β. EA treatment also restored the balance between Th1 and Th2 systems by increasing TNF-α and decreasing IL-4.”

Thus depression involves inflammation, but the cytokine expression can vary.

This topic is multifaceted and a proper synopsis of the functional approach to depression is too long for this forum, but here’s one more paper to keep the horizon open. This study published not long ago in the Journal of Psychiatric Practice investigates the role of low testosterone in depression.

“Studies suggest that testosterone (TT) replacement may have an antidepressant effect in depressed patients…The objective of this study was to explore the effect of TT administration on depression using both a systematic review of the literature and a meta-analysis.”

What did the data show?

“Meta-analysis of the data from these seven studies showed a significant positive effect of TT therapy on…depressed patients when compared with placebo. Subgroup analysis also showed a significant response in the subpopulations with hypogonadism…”

This certainly confirms expectations considering the population of testosterone receptors in the brain and their density in the frontal lobe. Hypogonadism means that the testicles are producing too little testosterone in response to stimulation by luteinizing hormone (LH). This validates my common sense practice of always including biologically active free fraction testosterone and LH in workups for male depression. Note: testosterone replacement, especially by a transdermal route (gel, patch, cream) can give a good initial result but end up back-firing. This is a topic for another post. For now just remember there is a better way.