A gaping hole in a review of nutritional psychiatry

This December 2016 Australian review published in September 2017 concerned:

“..the nutritional psychiatry field..the neurobiological mechanisms likely modulated by diet, the use of dietary and nutraceutical interventions in mental disorders, and recommendations for further research.”


The reviewers inexplicably omitted acetyl-L-carnitine, which I first covered in A common dietary supplement that has rapid and lasting antidepressant effects. A PubMed search on “acetyl carnitine” showed over a dozen studies from the past twelve months that were relevant to the review’s subject areas. Here’s a sample, beginning with follow-on research published in June 2016 of the study I linked above:

Reply to Arduini et al.: Acetyl-l-carnitine and the brain: Epigenetics, energetics, and stress

Dietary supplementation with acetyl-l-carnitine counteracts age-related alterations of mitochondrial biogenesis, dynamics and antioxidant defenses in brain of old rats

Neuroprotective effects of acetyl-l-carnitine on lipopolysaccharide-induced neuroinflammation in mice: Involvement of brain-derived neurotrophic factor

ALCAR promote adult hippocampal neurogenesis by regulating cell-survival and cell death-related signals in rat model of Parkinson’s disease like-phenotypes

Analgesia induced by the epigenetic drug, L-acetylcarnitine, outlasts the end of treatment in mouse models of chronic inflammatory and neuropathic pain

The cited references in these recent studies were older, of course, and in the time scope of the review. There’s no excuse for this review’s omission of acetyl-L-carnitine.

https://www.cambridge.org/core/journals/proceedings-of-the-nutrition-society/article/nutritional-psychiatry-the-present-state-of-the-evidence/88924C819D21E3139FBC48D4D9DF0C08 “Nutritional psychiatry: the present state of the evidence” (not freely available)

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Epigenetic effects of cruciferous vegetable compounds

This 2017 German review discussed the results of many of the studies performed over the past thirty years investigating the health-promoting effects of cruciferous vegetable compounds:

“SFN [sulforaphane] [is] the ITC [isothiocyanate] that is the most extensively studied for its chemopreventive and anti-inflammatory properties in vitro, as well as in vivo.

Due to the reversible nature of epigenetic aberrations, a modulation of epigenetically caused changes in gene expression by phytochemicals may be a promising approach in cancer prevention at the initiation step of carcinogenesis..Both SFN and DIM [di-indole methane] reversed many of the cancer-associated promotor methylations, including abnormally-methylated genes that are dysregulated during cancer progression..modulate the abnormal expression of miRNAs in different types of cancer.”

http://www.mdpi.com/1422-0067/18/9/1890/htm “Brassica-Derived Plant Bioactives as Modulators of Chemopreventive and Inflammatory Signaling Pathways”


A 2017 Polish human cell study that wasn’t cited above due to its recent publication found:

“We show for the first time that SFN is an epigenetic modulator in breast cancer cells that results in cell cycle arrest and senescence.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5596436/pdf/thnov07p3461.pdf “Sulforaphane-Induced Cell Cycle Arrest and Senescence are accompanied by DNA Hypomethylation and Changes in microRNA Profile in Breast Cancer Cells”

Parental lying thwarted both their children and researchers

This 2017 German human study explored the relationship between birth stress and handedness. The authors summarized previous research which, among other points, estimated epigenetic contributions to handedness as great as 75%.

The study hit a snag in its reliance on the sixty participants (average age 24) completing, with the assistance of their parents and medical records, a 24-item questionnaire of maternal health problems during pregnancy, substance use during pregnancy, and birth complications. The subjects didn’t provide accurate information. For example:

  • Only one of the subjects reported maternal alcohol use during pregnancy. An expected number would have been 26.
  • None of the subjects reported maternal mental illness during pregnancy. An expected number would have been at least 7.

The subjects’ parents willingly misled their children about facts of their child’s important earliest development periods. This is unethical to the children in that once it is recognized, it diminishes or destroys the society among family members. This study’s example is also of general interest to anyone who values not being lied to, like me.

As I mentioned on the Welcome page, lies and omissions ruin the standard scientific methodology of surveying parents and caregivers. The absence of evidence greatly increased the difficulty for researchers in determining causes of epigenetic effects still present in the subjects’ lives.

The parental lying is again unethical in that it diminished or destroyed the society between the sources of information – the research subjects – and the users of the information. It adversely affected anyone who values evidence-based research. The research hypothesis itself was worthwhile based on the prior studies cited and elsewhere such as Is what’s true for a population what’s true for an individual?.

http://www.tandfonline.com/doi/full/10.1080/1357650X.2017.1377726 “DNA methylation in candidate genes for handedness predicts handedness direction” (not freely available)

How one person’s paradigms regarding stress and epigenetics impedes relevant research

This 2017 review laid out the tired, old, restrictive guidelines by which current US research on the epigenetic effects of stress is funded. The reviewer rehashed paradigms circumscribed by his authoritative position in guiding funding, and called for more government funding to support and extend his reach.

The reviewer won’t change his beliefs regarding individual differences and allostatic load since he helped to start those memes. US researchers with study ideas to develop evidence beyond such memes may have difficulties finding funding.

Here’s one example of the reviewer’s restrictive views taken from the Conclusion section:

Adverse experiences and environments cause problems over the life course in which there is no such thing as “reversibility” (i.e., “rolling the clock back”) but rather a change in trajectory [10] in keeping with the original definition of epigenetics [132] as the emergence of characteristics not previously evident or even predictable from an earlier developmental stage. By the same token, we mean “redirection” instead of “reversibility”—in that changes in the social and physical environment on both a societal and a personal level can alter a negative trajectory in a more positive direction.”

What would happen if US researchers proposed tests of his “there is no such thing as reversibility” axiom? To secure funding, his sphere of influence would probably steer the prospective studies’ experiments toward altering “a negative trajectory in a more positive direction” instead. An example of his influence may be found in the press release of Familiar stress opens up an epigenetic window of neural plasticity where the lead researcher stated a goal of:

“..not to ‘roll back the clock’ but rather to change the trajectory of such brain plasticity toward more positive directions.”

I found nothing in citation [10] (of which the reviewer is a coauthor) where the rodent study researchers even attempted to directly reverse the epigenetic changes! The researchers under his guidance simply asserted:

“..a history of stress exposure can permanently alter gene expression patterns in the hippocampus and the behavioral response to a novel stressor”

without making any therapeutic efforts to test the permanence assumption! Never mind that researchers outside the reviewer’s sphere of influence have done exactly that. In any event, citation [10] didn’t support an “there is no such thing as reversibility” axiom.

The reviewer also implied that humans respond just like lab rats and can be treated as such. Notice that the above graphic conflated rodent and human behaviors. Further examples of this inappropriate merger of behaviors are in the Conclusion section.


What may be a more promising research approach to human treatments of the epigenetic effects of stress now that it’s 2017? I pointed out in The current paradigm of child abuse limits pre-childhood causal research:

“If the current paradigm encouraged research into treatment of causes, there would probably already be plenty of evidence to demonstrate that directly reducing the source of the damage would also reverse the damaging effects. There would have been enough studies done so that the generalized question of reversibility wouldn’t be asked.

Aren’t people interested in human treatments of originating causes so that their various symptoms don’t keep bubbling up? Why wouldn’t research paradigms be aligned accordingly?”

http://journals.sagepub.com/doi/full/10.1177/2470547017692328 “Neurobiological and Systemic Effects of Chronic Stress”

Epigenetic stress effects in preterm infants

This 2017 Italian review selected 9 human studies on the epigenetic effects of:

“..one of the major adverse events in human development. Preterm infants are hospitalized in the Neonatal Intensive Care Unit where they are exposed to life-saving yet pain-inducing procedures and to protective care.”

Highlights of the referenced studies included:

  • “..early exposure to adverse events during the third trimester of pregnancy is capable to alter the epigenetic status of imprinted and placenta-related genes which have relevant implications for fetal development and preterm infants’ HPA [hypothalamic–pituitary–adrenal] stress reactivity during infancy.”
  • “..there was an association between DNAm [DNA methylation] and white matter tract tissue integrity and shape inferred from dMRI [diffusion MRI], suggesting that epigenetic variation may contribute to the cerebral phenotype of preterm birth.”

Limitations of the referenced studies included:

  • “A multiple sampling design that includes parental samples, placental tissue, cord blood and extends across the life-course would be required to investigate the relative contributions of in utero and postnatal exposures to changes in DNAm, and the extent to which preterm birth leaves a legacy on the methylome.”
  • Saliva, blood, and other tissues’ DNA methylation may not produce valid links to brain tissue DNA methylation of the same gene, which may hamper conclusive inferences about behavior, etc.

http://www.sciencedirect.com/science/article/pii/S0149763417302117 “Preterm Behavioral Epigenetics: A systematic review” (not freely available)

http://www.nature.com/tp/journal/v6/n1/full/tp2015210a.html “Epigenomic profiling of preterm infants reveals DNA methylation differences at sites associated with neural function” (one of the studies selected, quoted above)