Issue 99

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Here's another awesome issue of the Science Digest, curated just for you, our Premium
Members. We've covered a wide range of topics related to health, fitness, and aging.
Read on to learn how...
Extreme microdose of THC from cannabis (three to four orders of magnitude
lower than standard dose) produces long-term neuroprotection in mice subjected
to acute neurological insults.
New study reveals a critical role for the gut-brain axis in infant brain development.
Ketogenic diet may alleviate ADHD symptoms by altering gut microbiota and
boosting neurotransmitter expression.
And more!

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Science Digest - August 25, 2023

Extreme microdose of THC from cannabis (three to four orders of

magnitude lower than standard dose) produces long-term
neuroprotection in mice subjected to acute neurological insults.
Delta-9-tetrahydrocannabinol – better known as THC – is the primary psychoactive
compound found in cannabis. THC binds to endocannabinoid system receptors, eliciting
a wide range of physical effects and producing the “high” associated with its use. A new
study suggests that THC reverses brain aging in old mice.
Researchers injected old mice with a microdose of THC that was roughly three to four
orders of magnitude lower than a typical dose. Then, they assessed gene expression in
the animals' hippocampal tissue at five days and five weeks post-treatment.

After just five days, they found that the microdose THC treatment altered the expression
of 18 genes related to neurogenesis (the production of new nerve cells). THC altered the
expression of 88 genes related to nerve cell survival and development five weeks post-
treatment. Interestingly, THC did not affect brain-derived neurotrophic factor, a protein
noted for its effects on neurogenesis.

These findings suggest that a single microdose of THC exerts potent, enduring effects
on the rodent brain and may have potential applications in humans. It also aligns with
results from a compelling case study in which THC microdosing ameliorated symptoms
of Alzheimer’s disease. Lactate, a molecule produced during vigorous exercise, also has
robust effects on the brain, influencing neurogenesis and promoting cognitive function.
Learn more in this episode featuring Dr. George Brooks.

Read full publication.

Infant gut microbes including Actinobacteria and Bifidobacterium linked

to improved social attention tests, suggesting a role for the microbiome
in early cognitive development.
The gut-brain axis is a complex communication system that links the gut microbial
community, digestive system, and nervous system. A new study shows that the gut-brain
axis plays a critical role in brain development. Infants demonstrating specific patterns of
enhanced brain activity, such as rhythmic processing, exhibited unique gut microbial
populations and metabolic processes.

Researchers analyzed the microbial composition of fecal samples collected from 56

infants between the ages of four and six months. They evaluated the infants' brain
activities via electroencephalogram (EEG) while the infants listened to a rhythmic beat.
Then, using behavioral tests, they assessed aspects of the infants' cognitive abilities,
including neural rhythm tracking, language discrimination, and joint attention.

Neural rhythm tracking facilitates information organization across time, influencing

perception, social communication, language, and cognition. Language discrimination
differentiates between language and non-language. Joint attention is a social skill that
influences infants' capacity to learn from others, affecting early language acquisition and
overall cognition.
They found that infants who performed well in the joint attention test exhibited specific
gut microbial patterns that included higher numbers of Actinobacteria, Bifidobacterium,
and Eggerthella, and lower numbers of Firmicutes, Hungatella, and Streptococcus. The
EEGs revealed unique neural activity patterns associated with enhanced rhythmic
processing, which varied according to the presence of specific microbes. In addition,
these neural activity patterns were associated with upregulated metabolic processes
involving microbes linked with neurodevelopment.

This study was small; however, its findings suggest a potential connection between the
gut microbiome and early cognitive development. It also highlights the intricacies of the
gut-brain axis, with potential implications for understanding early brain development and
cognitive function. Learn more about the role of the gut microbiota in this episode
featuring Drs. Erica and Justin Sonnenburg.

Read full publication.

Ketogenic diet may alleviate ADHD symptoms by altering gut

microbiota and boosting neurotransmitter expression.
Attention deficit hyperactivity disorder (ADHD) is a common neurobehavioral condition
observed in children and adults. A recent study in mice suggests that a ketogenic diet
reduces symptoms of ADHD via alterations in the gut microbiota.

Researchers conducted experiments using two groups of rats: one with ADHD-like
symptoms and another without. They further divided each group into three subgroups:
those fed a standard diet, those treated with methylphenidate (an ADHD drug commonly
sold as Ritalin, Concerta, or others), and those fed a ketogenic diet.

They found that both the methylphenidate and ketogenic diet interventions reduced
ADHD-like behaviors, such as increased activity and hypermobility. In addition, both
groups demonstrated elevated levels of various neurotransmitters, including serotonin,
norepinephrine and others, in brain tissue, along with changes in the expression of key
proteins related to neural signaling. Interestingly, the ketogenic diet also altered the gut
microbial composition in ADHD-like rats, especially microbes involved in amino acid and
sugar metabolism.

These findings suggest that the ketogenic diet may hold promise as a novel approach for
mitigating ADHD-related behavioral challenges, possibly by influencing the gut
microbiota. It also underscores the robust effects the ketogenic diet has on the brain.
Learn more in this clip featuring Dr. Dominic D'Agostino.
 Read full publication.

Time-restricted feeding corrects Alzheimer’s disease circadian

disruptions in mice, reducing amyloid protein accumulation and
improving memory.
Alzheimer’s disease is the most common form of dementia, affecting more than 55
million people worldwide. People with Alzheimer’s disease often experience altered
circadian rhythms, manifesting as altered sleep/wake cycles and difficulty in falling and
staying asleep. A new study in mice suggests that time-restricted eating restores
normal circadian rhythmicity and reduces amyloid plaque formation in the brain.

Using a mouse model of Alzheimer’s disease, researchers gave one group of mice free
access to food throughout the day but fed another group on a time-restricted schedule
(limited to a six-hour window each day), translating to about 14 hours of fasting for
humans. Then, they evaluated the animals' gene expression, amyloid-beta
accumulation, and cognitive performance.

They found that the mice fed on the time-restricted schedule had better memory
function, were less hyperactive at night, followed a more regular sleep schedule, and
experienced fewer disruptions during sleep than the mice allowed free access to food.
The restricted mice also performed better on cognitive assessments and exhibited less
amyloid accumulation in the brain. Time-restricted feeding also normalized gene
expression in the hippocampus, an area of the brain involved in memory and often
affected by Alzheimer’s disease.

These findings suggest that time-restricted eating mitigates the behavioral symptoms
and pathological features associated with Alzheimer’s disease. Robust evidence
indicates that time-restricted eating influences multiple aspects of human health. Learn
more about time-restricted eating in this clip featuring Dr. Satchin Panda.

Read full publication.

Breast milk lipid molecule stimulates brain stem cells to produce

oligodendrocytes, effectively reversing white matter damage in neonatal
mice.
Premature infants are at greater risk for developing cerebral palsy, a motor disability
caused by brain injury-related white matter losses, impairing movement, balance, and
posture. However, a new study in mice indicates that a cholesterol-like molecule present
in breast milk may protect against cerebral palsy. Mice administered breast milk were
protected from the harmful effects of white matter losses.
protected from the harmful effects of white matter losses.

Researchers tested the ability of several oxysterols (naturally occurring cholesterol-like

molecules) in human breast milk to promote the production of oligodendrocytes, a type
of cell that stimulates white matter development. They found that the oxysterol 20-alpha
hydroxycholesterol induced oligodendrocyte production through the sonic hedgehog
pathway – a well-known pathway involved in neurodevelopment.

Then, they gave neonatal mice that had experienced inflammation-driven brain injury
and subsequent white matter losses 20-alpha hydroxycholesterol. They found that the
compound promoted white matter formation, reversing the animals' brain injuries.
These findings suggest that 20-alpha hydroxycholesterol, a compound present in breast
milk, influences neonatal white matter development and may benefit infants at risk for
cerebral palsy or other brain injury-related disorders. Learn more about the benefits of
breast milk in our overview article.

Read study abstract.

Ovarian cancer tumors, even at advanced stages, may be effectively

targeted and eliminated by CAR-T immune therapies, a new study in
mice suggests.
CAR-T, or chimeric antigen receptor T-cell therapy, is an immunotherapy approach that
involves genetically modifying a person’s own T cells so they can recognize and target
specific proteins on cancer cell surfaces, enhancing the immune system’s capacity to
seek out and destroy malignant cells. CAR-T therapies have been successful against
blood cancers, such as leukemia, lymphoma, or myeloma, but have largely failed with
solid tumors. Now, a new study in mice demonstrates that CAR-T is effective against
ovarian cancer, nearly doubling survival time.

Researchers identified a unique carbohydrate present only on the surface of solid tumor
cells, not healthy ones, and engineered CARs with a strong affinity for the carbohydrate.
Then, they delivered the CAR-T therapy via intravenous injection to mice with ovarian
cancer. Because ovarian cancer treatments delivered directly into the abdominal area
are particularly effective, they also administered the CAR-T therapy into the animals'
abdomens.

They found that the CAR-equipped T cells effectively located and eliminated the cancer
cells, promoting tumor shrinkage or elimination with just one dose. The genetically
engineered cells maintained their effectiveness for several months, with no evidence of
toxicity or adverse effects. Intravenous injection of CAR-T cells increased survival to 145
days, but direct delivery into the animals' abdomens extended survival to 270 days.
days, but direct delivery into the animals' abdomens extended survival to 270 days.

These findings demonstrate that modified CAR-T cells show promise as a potential
treatment for ovarian cancer and other solid tumors. Future studies are needed to
assess the treatment’s effectiveness in humans. Learn more about genetic engineering
in this episode featuring Dr. George Church.

Read study abstract.

Chronic cold exposure reduces tumor growth by 80 percent and

doubles survival rates in mice.
Cancer treatments often target glucose uptake to impede tumor growth, primarily
through pharmaceuticals, many of which exert considerable side effects. However, cold
exposure is emerging as a potential alternative to these drug-based therapies. A recent
study in mice found that cold exposure reduced tumor growth by 80 percent and
increased survival rates twofold.

Researchers conducted a two-part study in mice and humans. First, they exposed mice
with cancer to cold (4°C, 39°F) or thermoneutral (30°C, 86°F) temperatures for about
three weeks. They found that the cold exposure activated the animals' brown fat,
depleting the energy supply available to the tumors. The cold-exposed mice exhibited
marked tumor growth inhibition and a nearly twofold increase in survival rates relative to
the thermoneutral mice. Interestingly, when they fed the cold-exposed mice a high-
glucose diet, the animals did not experience the same extent of tumor growth inhibition,
suggesting that glucose scarcity was pivotal in suppressing cancer growth.

In the second part of the study, they exposed healthy people to cool temperatures (16°C,
61°F) for two to six hours per day for 14 days and found that the participants
experienced brown fat activation similar to the mice. Then, they exposed a person with
Hodgkin’s lymphoma to cool (22°C, 71°F) temperatures for seven days and found that
the participant exhibited activated brown fat and their tumor showed diminished glucose
consumption, suggesting the findings in mice translate to humans.

These findings suggest that cold exposure activates brown fat, reducing blood glucose
and impeding tumor growth. Brown fat is a thermogenic (heat-producing) tissue. Studies
in animals and humans suggest that brown fat can improve glucose and insulin
sensitivity, increase fat oxidation, and protect against diet-induced obesity. Cold
exposure increases brown fat volume and metabolism and drives glucose uptake. Learn
more about cold exposure and its effects on brown fat in our overview article.

Read full publication.

 Read full publication.

Breastfeeding for six months or more may reduce the risk of maternal
cardiovascular problems for at least three years after delivery,
according to new study.
Breastfeeding benefits mothers by promoting post-partum weight loss and reducing the
risk of certain types of cancer later in life. A new study suggests that breastfeeding also
supports maternal cardiometabolic health. Women who breastfed for at least six
months were leaner and had lower blood pressure than those who didn’t.

Researchers conducted health check-ups on 160 mother-child pairs enrolled in

Screening Tests to Predict Poor Outcomes of Pregnancy, a long-term study that
assessed women’s risk for pregnancy complications. They assessed the women’s
cardiometabolic health via blood pressure, body measurements, and serum metabolic
markers (glucose and lipids). They determined breastfeeding duration via the children’s
health records.

They found that the cardiometabolic health of women who breastfed for at least six
months was considerably better than those who did not breastfeed, as evidenced by
lower body mass index (BMI) and blood pressure. These differences persisted even after
considering factors like BMI, socioeconomic status during early pregnancy, prenatal
smoking, and maternal age during early pregnancy. In women who had experienced
pregnancy complications (such as preeclampsia or gestational diabetes), breastfeeding
for at least six months reduced blood pressure, insulin, and triglycerides, while
increasing HDL cholesterol levels.

These findings suggest that breastfeeding for a minimum of six months benefits the
cardiovascular health of mothers, particularly those who experienced pregnancy
complications. They also highlight the importance of breastfeeding as a potential means
to reduce the risk of cardiovascular issues in women following childbirth. However, the
investigators conceded that this was a small study, potentially hindering its translatability
to a broad audience. Learn more about the maternal benefits of breastfeeding in our
overview article.

Read full publication.