Image by Chen from Pixabay

September 9, 2023

Literature Review

1) "Attention deficit hyperactivity disorder (ADHD) is a common mental behavioral disorder in children. Alterations in gut microbiota composition are associated with neurological disorders.

We aimed to investigate whether a ketogenic diet (KD) can be an alternative therapy for ADHD by altering the gut microbiota. Male spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats were randomly allocated to the normal diet (ND), methylphenidate (MPH), and KD groups. SHR in groups KD and MPH exhibited a significant increase in behavioral characteristics of ADHD, such as distance moved and immobility time. KD and MPH treatment led to a significant elevation in concentrations of 5-HT, AC, cAMP, and NE of brain tissue and the expression of DRD1, DAT, PKA, DARPP32, and cAMP at the protein level in WKY rats and SHR. KD and MPH significantly increased the richness and diversity of gut microbiota in SHR. The abundance of Ruminococcus_gauvreauii_groupBacteroidesBifidobacterium, and Blautiasignificantly increased, whereas that of LactobacillusRomboutsiaFacklamia, and Turicibactersignificantly declined in the KD group compared with the ND group. The gut microbiota in the KD group of SHR mainly participated in amino acid metabolism- and sugar metabolism-related pathways. KD might alleviate behavioral disorders in ADHD by regulating gut microbiota. This study provides novel insights for the use of KD in treating ADHD." (Liu et. al. 2023)

For me this study is more about the diet that was the control as opposed to the ketogenic diet in and of itself. It is clear to me that ketogenic diets are neuron sparing whether it is neurodegenerative disease or seizures. However, the issue for ADHD in my mind is the highly processed, highly sugar laden substrates that drive neuronal damage in the average American student. Other than being a very difficult diet to follow ( I have tried for a week ), the ketogenic diet is safe for all to experiment with.

2) A new covid paper looking at reinfection over time based on prior natural disease sheds some light on real time statistics. From the Lancet: "protection from past infection and any symptomatic disease was high for ancestral, alpha, beta, and delta variants, but was substantially lower for the omicron BA.1 variant. Pooled effectiveness against re-infection by the omicron BA.1 variant was 45·3% and 44·0% against omicron BA.1 symptomatic disease. Mean pooled effectiveness was greater than 78% against severe disease (hospitalisation and death) for all variants, including omicron BA.1. Protection from re-infection from ancestral, alpha, and delta variants declined over time but remained at 78·6% at 40 weeks. Protection against re-infection by the omicron BA.1 variant declined more rapidly and was estimated at 36·1% at 40 weeks. On the other hand, protection against severe disease remained high for all variants, with 90·2% for ancestral, alpha, and delta variants, and 88·9% for omicron BA.1 at 40 weeks." (Covid forecasting team 2023)

What we glean from this data set is that human infection with the Omicron variants are more difficult to remain immune to symptomatically over a years time course but remain highly protective against severe disease. This continues to pigeon hole current Sars2 infection in the land of influenza with mostly mild disease and as discussed last week a reasonable reproductive rate of just over 1. In children, Sars2 is utterly benign. We have yet to see a significant case requiring intervention beyond that of a common cold or flu case.

3) A combination of omega 3 and 6 fatty acids did not improve premature born infants vision. From the study: "Of 178 children in the trial, 115 (with median gestational age (GA) of 25 + 4/7 weeks and median birth weights of 790 g) were ophthalmologically assessed at a median corrected age of 2.7 years (range 2.0–3.9 years). VA assessment was missing in 42.1% (75/178), in 41.7% (35/84) of the AA/DHA supplemented infants, and in 42.6% (40/94) of the control infants. After MI and adjustments for GA, study center, plurality, and corrected age at VA exam, no significant effect of AA/DHA supplementation was detected in VA outcome (≥20/63) (odds ratio 2.16, confidence interval 95% 0.99–4.69, p = 0.053).(Lungren P. et. al. 2023) It is always useful to publish and discuss negative findings as much as positive. In this case the authors found no benefit. The study, to me, is flawed from the start as the supplement was a mix of AA and DHA. The issue here is that AA is not a deficienct fatty acid in the human population of pregnant women. The omega 3 fatty acids are the concern. Thus, a null finding is not surprising. The other concern I have with the study is the 50% patient volume loss over the study period.

The mechanism of affect for DHA and EPA fatty acids would be protection of the visual neurons and cells from oxidative stress and inflammation associated with prematurity and retinopathy of prematurity.

4) Neurological finding in a cohort of post concussed individuals is discussed in a new JAMA study. This is very important albeit sad data set from the Understanding Neurologic Injury and Traumatic Encephalopathy (UNITE) Brain Bank of young donated athlete brains. From the study: "In this case series of 152 contact sport athletes younger than 30 years at the time of death, chronic traumatic encephalopathy (CTE) was found in 63 (41.4%), with nearly all having mild CTE (stages I and II). Neuropathologic abnormalities associated with CTE included ventricular enlargement, cavum septum pellucidum, thalamic notching, and perivascular pigment–laden macrophage deposition in the frontal white matter." (McKee A. et. al. 2023)

The follow up findings were striking . The cause of death was CTE related in almost all cases from suicide or drug overdose. All CTE sufferers were neurologically symptomatic. 75% were male and football was the most common sport associated with a bad outcome. Repetitive head traumas in a susceptible population playing contact sports is a major concern for all of us in medicine and parents. I cannot stress enough that nutrition, omega 3 fatty acids, sleep and general health are protective against inflammation in the entire system. Problem number one remains protective gear and playing style in contact sports. We must continue to invest in preventative measures for those that continue to engage in sport. However, controlling the inputs to systemic inflammation are of significant importance as well. More to come.

5) Continued evidence has shown that the bacterial intestinal microbiome is associated with neurological health in infants and children. This bacterial population is delivered by the mother and altered by diet and drug exposure primarily in the early period of life. Bacterial colonization occurs before the maturation of many neural systems of the infant. In PLOSOne, we see: "study with a multidisciplinary approach to test if the microbiota composition of infants is associated with measures of early cognitive development, in particular neural rhythm tracking; language (forward speech) versus non-language (backwards speech) discrimination; and social joint attention... Infants who succeeded at the Point and Gaze test tended to have increased Actinobacteria and reduced Firmicutes at the phylum level; and an increase in Bifidobacterium and Eggerthella along with a reduction in Hungatella and Streptococcus at the genus level. Measurements of neural rhythm tracking associated negatively to the abundance of Bifidobacterium and positively to the abundance of Clostridiumand Enterococcus for the bacterial abundances, and associated positively to metabolic pathways that can influence neurodevelopment, including branched chain amino acid biosynthesis and pentose phosphate pathways." (Hunter et. al. 2023)

This is a small study, but again points to the same reality, the bacteria are here for a symbiotic relationship. We need to heed this data for mothers primarily to understand the risk of current human lifestyle decisions as they relate to diets, medicine exposure, chemicals and more.

That's it for today,

Dr. M


Covid Forecasting Team Lancet

Lundgren Lancet


Solano Cell Immunity

Hunter PLOSOne