“During the past 2 decades, celiac disease (CD) has been recognized as a multisystem autoimmune disorder. A growing body of distinct neurologic conditions such as cerebellar ataxia, epilepsy, myoclonic ataxia, chronic neuropathies, and dementia have been reported, mainly in middle-aged adults…The aim of the present study is to look for a broader spectrum of neurologic disorders in CD patients, most of them children or young adults.”

They found a much greater prevalence of neurological disorders in children with CD compared to normal controls: 51.4% to 19.9%, including hypotonia, developmental delay, learning disorders and ADHD, headache, and cerebellar ataxia.

The authors conclude:

“This study suggests that the variability of neurologic disorders that occur in CD is broader than previously reported and includes “softer” and more common neurologic disorders, such as chronic headache, developmental delay, hypotonia, and learning disorders or ADHD.”

Bear in mind that we are equally concerned with the neurologic manifestations of gluten sensitivity in the absence of celiac disease.

“Binge alcohol consumption in adolescents is increasing, and studies in animal models show that adolescence is a period of high vulnerability to brain insults. The purpose of the present study was to determine the deleterious effects of binge alcohol on hippocampal neurogenesis…”

The authors made a number of startling observations regarding the effect of alcohol on the brain’s center for short-term memory and adrenal regulation, the hippocampus:

“Heavy binge alcohol consumption over 11 mo dramatically and persistently decreased hippocampal proliferation and neurogenesis…Alcohol significantly decreased the number of actively dividing type 1, 2a, and 2b cell types…suggesting that alcohol interferes with the division and migration of hippocampal preneuronal progenitors. Furthermore, the lasting alcohol-induced reduction in hippocampal neurogenesis paralleled an increase in neural degeneration mediated by nonapoptotic pathways.”

Yikes. The authors sum up their findings with these memorable comments:

“Altogether, these results demonstrate that the hippocampal neurogenic niche during adolescence is highly vulnerable to alcohol… This lasting effect, observed 2 mo after alcohol discontinuation, may underlie the deficits in hippocampus-associated cognitive tasks that are observed in alcoholics.”

A fascinating paper published last month in the Journal of Neuroscience now reveals how alcohol feeds an immune inflammatory attack on the brain:

“Toll-like receptors play an important role in the innate immune response, although emerging evidence indicates their role in brain injury and neurodegeneration. Alcohol abuse induces brain damage and can sometimes lead to neurodegeneration. We recently found that ethanol can promote TLR4 signaling in glial cells by triggering the induction of inflammatory mediators and causing cell death, suggesting that the TLR4 response could be an important mechanism of ethanol-induced neuroinflammation.”

This is an extremely persuasive argument for moderation for anyone interesting in preserving brain health.

The authors go on to report that TLR4 is critical for ethanol-induced inflammatory signaling in glial cells by demonstrating that ‘turning off’ TLR4 prevents the neuroinflammatory brain damage:

“Our results demonstrate, for the first time, that whereas chronic ethanol intake upregulates…cytokine levels [interleukin (IL)-1β, tumor necrosis factor-{alpha}, IL-6] in the cerebral cortex,…TLR4 deficiency protects against ethanol-induced glial activation, induction of inflammatory mediators, and apoptosis. Our findings support the critical role of the TLR4 response in the neuroinflammation, brain injury, and possibly in the neurodegeneration induced by chronic ethanol intake.”

For us the main message is that excessive alcohol consumption fires up the brain’s glial cells (immune cells) and the resultant neuroinflammation does serious damage to the brain. This important research was highlighted in an editorial published last week in Science Translational Medicine which contains some notable comments:

“Ethanol is the most widely used psychotropic substance in the world, and chronic ethanol abuse leads to harmful changes in virtually every organ system in the body. Notably, this includes the brain, where consumption of alcohol can lead to irreversible changes in cognition, mood, and behavior. Although it has been known that this often involves degenerative, inflammatory-mediated processes, their precise nature has not been characterized. In a recent article, Alfonso-Loeches and colleagues report that much of the ethanol-induced inflammation in the brain depends on signaling through Toll-like receptors (TLRs). These receptors participate in innate immunity responses to infection but are also implicated in reactions to injury and degeneration in the brain.”

The editorial concludes with the compelling comparison of the brain damage done by activation by alcohol of neuroinflammation through Toll-like receptors with other common neurodegenerative conditions:

“These results suggest that TLRs play a critical role in alcohol-related brain changes, just as they have been previously implicated in Alzheimer’s disease, ischemic brain injury, and HIV infection.”

Besides curtailing excess and enjoying alcohol only in moderation we may be able to use coffee as protective therapy. There is abundant evidence of the benefit of coffee for the liver, including this recent study published in the journal Inflammation Research. The authors present data that:

“Treatment with caffeine significantly attenuated the elevated serum aminotransferase enzymes and reduced the severe extent of hepatic cell damage, steatosis and the immigration of inflammatory cells… Furthermore, caffeine decreased serum and tissue inflammatory cytokines levels, tissue lipid peroxidation and inhibited the necrosis of hepatocytes. Kupffer cells isolated from ethanol-fed mice produced high amounts of reactive oxygen species (ROS) and tumor necrosis factor alpha (TNF-α), whereas Kupffer cells from caffeine treatment mice produced less ROS and TNF-α.”

The authors conclude:

“These findings suggest that caffeine may represent a novel, protective strategy against alcoholic liver injury by attenuating oxidative stress and inflammatory response.”

Could this protective effect extend to the brain? There’s a lot of emerging evidence that suggests the answer is ‘yes’. Fascinating research published last month in the journal Experimental Neurology demonstrates that caffeine protects the brain from the kind of damage involved in Parkinson’s disease caused by pesticides:

“Environmental exposures suspected of contributing to the pathophysiology of Parkinson’s disease (PD) include potentially neurotoxic pesticides, which have been linked to an increased risk of PD. Conversely, possible protective factors such as…caffeine have been linked to a reduced risk of the disease. Here we assessed whether caffeine alters dopaminergic neuron loss induced by exposure to environmentally relevant pesticides (paraquat and maneb) over 8 weeks.”

The data led to a conclusion that increases my enthusiasm for exercising the French press:

“Caffeine at 20 mg/kg significantly reduced TH+ neuron loss (to 85% of the respective control). The results demonstrate the neuroprotective potential of caffeine in a chronic pesticide exposure model of model of PD.”

As for Alzheimer’s disease, a supplemental issue of the Journal of Alzheimer’s Disease has no less than 22 papers on the benefits of caffeine for AD and other neurodegenerative disorders. I suggest you have a look, drink alcohol in moderation (or not at all if you prefer), and enjoy your coffee and tea if there are no contraindications.

With alcohol, as with so many other substances and stimuli, we can appreciate the principle of hormesis: a small amount may have benefit while a larger amount is harmful.

“We examined the association between adolescent fiber intake and proliferative BBD [benign breast disease], a marker of increased breast cancer risk, in the Nurses’ Health Study II.”

They gathered data on diet and the emergence of breast disease confirmed by pathology for 29,480 females. A definite pattern emerged:

“Women in the highest quintile of adolescent fiber intake had a 25% lower risk of proliferative BBD… High school intake of nuts was also related to significantly reduced BBD risk. Women consuming ≥2 servings of nuts/week had a 36% lower risk…than women consuming <1 serving/month.”

Taking into consideration other research I think we have to accept the likelihood that the beneficial fat in nuts confers some of the benefit. This adds to the weight of evidence in favor of nuts in a wholesome and preventative diet:

“These findings support the hypothesis that dietary intake of fiber and nuts during adolescence influences subsequent risk of breast disease and may suggest a viable means for breast cancer prevention.”

“Historically, the relationship between diet and acne has been highly controversial. Before the 1960s, certain foods were thought to exacerbate acne. However, subsequent studies dispelled these alleged associations as myth for almost half a century. Several studies during the last decade have prompted dermatologists to revisit the potential link between diet and acne.”

Thankfully the perspective is becoming more realistic:

“Dermatologists can no longer dismiss the association between diet and acne.”

Although much work remains to be done in order to make evidence based recommendations pertaining to various dietary factors and acne, on thing is clear:

“Compelling evidence exists that high glycemic load diets may exacerbate acne.”

This is not surprising considering the inflammatory and hormonal consequences of overstimulating insulin production.

“Maternal infection during pregnancy has been associated with increased incidence of schizophrenia in the adult offspring. Mechanistically, this has been partially attributed to neurodevelopmental disruption of the dopamine neurons, as a consequence of exacerbated maternal immunity. In the present study we sought to target hypoferremia, a cytokine-induced reduction of serum non-heme iron, which is common to all types of infections. Adequate iron supply to the fetus is fundamental for the development of the mesencephalic dopamine neurons and disruption of this following maternal infection can affect the offspring’s dopamine function.”

The authors measured the adverse behavioral and neurochemical changes from challenging the dopamine circuits with turpentine to trigger an inflammatory immune response, both with and without maternal iron supplementation. They demonstrated that…

“Both the behavioral and neurochemical changes were prevented by maternal iron supplementation.“

We already know that iron is a critical nutrient for dopamine production in the adult. Their conclusion sums up why prenatal iron status is important in preventing neurodevelopmental disorders including schizophrenia in the offspring.

“Emerging evidence suggests that docosahexaenoic acid (DHA, 22:6n–3)…positively regulates cortical metabolic function and cognitive development…The objective was to determine the effects of DHA supplementation on functional cortical activity during sustained attention in human subjects.”

After giving the randomly assigned test cohort DHA supplements they compared cortical activation patterns during sustained attention with those given placebo by functional magnetic resonance imaging (fMRI).

What did their data show?

“At 8 wk, erythrocyte [red blood cell] membrane DHA composition increased significantly from baseline in subjects who received low-dose (by 47%) or high-dose (by 70%) DHA but not in those who received placebo (–11%). During sustained attention, both DHA dose groups had significantly greater changes from baseline in activation of the dorsolateral prefrontal cortex than did the placebo group…The erythrocyte DHA composition was positively correlated with dorsolateral prefrontal cortex activation…”

That last phrase is especially important: DHA is not the only fatty acid that is important for neuronal (brain cell) function. EPA, arachadonic acid and others also play important roles. How do we know with certainty whether someone needs supplementation, which fatty acid should it be, and how much? The Essential Fatty Acid Profile measures the red blood cell membrane content of fatty acids (and is equivalent to the neuronal membrane composition) that we use is the lab technology used by these investigators.

The authors’ conclusion:

“Dietary DHA intake and associated elevations in erythrocyte DHA composition are associated with alterations in functional activity in cortical attention networks during sustained attention in healthy boys.”

For any brain-related disorder we need to objectively answer the questions “What is the brain fatty acid composition? Are there any deficiencies or imbalances? Is supplementation indicated?” When needed, the correct fatty acid supplementation can result in dramatic improvements.

“Coeliac disease in adolescents has been associated with an increased prevalence of depressive and disruptive behavioural disorders, particularly in the phase before diet treatment.”

We are equally concerned with the ‘non-celiac’ aspects of gluten sensitivity. Gluten related inflammation in the brain can manifest as a host of cognitive, emotional and neurodegenerative disorders in the absence of intestinal manifestations. This is often referred to as “silent celiac disease”:

“Coeliac disease is an under-diagnosed autoimmune type of gastrointestinal disorder resulting from gluten ingestion in genetically susceptible individuals. Non-specific symptoms such as fatigue and dyspepsia are common, but the disease may also be clinically silent.”

They further note that:

“”Depressive symptoms and disorders are common among adult patients with coeliac disease, and depressive and disruptive behavioural disorders are highly common also among adolescents, particularly in the phase before diet treatment. Recently 73% of patients with untreated coeliac disease – but only 7% of patients adhering to a gluten-free diet – were reported to have cerebral blood flow abnormalities similar to those among patients with depressive disorders.”

Their data revealed abnormalities in tryptophan assimilation (tryptophan is the amino acid precursor to serotonin) and prolactin levels in adolescents with celiac disease and depression prior to treatment. Consequently…

“A significant decrease in psychiatric symptoms was found at 3 months on a gluten-free diet compared to patients’ baseline condition, coinciding with significantly decreased coeliac disease activity…”

They also make a fascinating observation that links gluten sensitivity, inflammation, and the serotonergic aspect of depression unrelated to malabsorption:

“…increased production of interferon-γ (IFN-γ), known to be the predominant cytokine produced by gluten-specific T-cells in active coeliac disease, can suppress serotonin function both directly and indirectly by enhancing tryptophan and serotonin turnover…even without malabsorption.”

To diagnose gluten sensitivity in the absence of celiac disease the gluten gene sensitivity test is the most reliable method for a number of reasons.

“Maternal nutrition during pregnancy has been linked with fetal brain development and psychopathology in the offspring. We examined for associations of maternal folate status and dietary intake during pregnancy with brain growth and childhood behavioural difficulties in the offspring.”

They correlated maternal red blood cell folate (RCF) at 14 weeks of pregnancy and total folate intake (TFI) from food and supplements with their childrens’ behavioral difficulties. What did the data show?

“Lower maternal RCF and TFI in early pregnancy were associated with higher childhood hyperactivity and peer problems scores in the offspring….analyses showed significant inverse indirect associations of RCF with hyperactivity/inattention and peer problems via fetal brain growth.”

Their conclusion:

“…our data provide preliminary support for the hypothesis that lower folate status in early pregnancy might impair fetal brain development and affect hyperactivity/inattention and peer problems in childhood.”

Here we have another compelling reason to ascertain good folate status in early pregnancy, or (even better) before becoming pregnant. Although conventional blood tests for serum folate are not dependable, a convenient and reliable way to do determine folate adequacy is by measuring the organic acid formiminoglutamate in the urine.

“Sleep position is an important safety issue for infants younger than 1 year. This is because sudden infant death syndrome (SIDS) is associated with infants sleeping on their tummies. Sudden infant death syndrome is the leading cause of death for infants younger than 1 year. It most commonly occurs in babies between the ages of 2 and 4 months. Despite more than 15 years of the “back to sleep” educational campaign, some parents still are not provided with appropriate education about the safest sleep position for babies.”

The authors of the study itself interviewed approximately 1000 nighttime caregivers of infants per year over a fifteen year period to determine whether or not the infant is usually placed on his or her back to sleep. Although the message has gotten out in the past decade or so, too many parents remain misled due to…

“…concern about comfort, choking, and [misleading] advice.”

It is not difficult  for health professionals with training and experience in the management of cranial and upper cervical conditions to understand how rotation of the head to the side while prone would result in mechanical stress to the vulnerable infant respiratory centers (through torque on the delicate brain stem and its meningeal covering). The authors note in their conclusion:

“To decrease sudden infant death syndrome rates, we must ensure that public health measures reach the populations at risk and include messages that address concerns about infant comfort and choking.”

“In developed countries, every child will present to a primary health-care practitioner more than once every year with symptoms of an acute infection. Primary care physicians faced with such a child know that the likelihood of serious disease is about 1%, but what has not been clear is the evidence-based approach that clinicians should take in investigating such children. In The Lancet today, Ann Van den Bruel and colleagues address this uncertainty…”

In other words, if your child has an acute infection, there is a 99% chance that it is not serious. But to catch the 1% that need a more aggressive intervention, the study identified these red flags:

“Cyanosis [bluish discoloration of skin, mucous membranes, nail beds, etc.], rapid breathing, poor peripheral perfusion [poor delivery of arterial blood to the capillaries—check the nail beds], and petechial rash were identified as red flags in several studies. Parental concern and clinician instinct were identified as strong red flags in one primary care study. Temperature of 40°C [104°F] or more has value as a red flag in settings with a low prevalence of serious infection. No single clinical feature has rule-out value but some combinations can be used to exclude the possibility of serious infection—for example, pneumonia is very unlikely if the child is not short of breath and there is no parental concern.”

Though this is not a fool-proof checklist, it is still worth bearing in mind:

1. Cyanosis (bluish discoloration)
2. Rapid breathing
3. Poor perfusion of blood in the extremities
4. Petechial rash (red-purple spots 1-2 mm in diameter)
5. Your instinct that something is seriously wrong
6. Persistent fever over 104°F (particularly with the above; remember that fever is a necessary part of the immune response).