How Food Choices Shape Memory, Cognition & Cravings | Dr. Scott Kanoski

Diet and Neurocognition in Rodent Models [00:00:00]

• Early studies focused on high-sugar diets, where animals consumed sugar solutions equivalent to soft drinks.
• These animals exhibited hippocampal-dependent memory deficits that persisted even after sugar consumption ceased.
• Research suggests a potential role for the gut microbiome in these memory impairments, with observed changes in gut bacteria.

  "There may be a role for the microbiome. There's some changes in the bacteria in the gut from the sugar model that may have a functional connection to the memory impairments."

Junk Food Diet and Lasting Memory Deficits [00:01:00]

• Models involving total junk food diets (chocolate peanut butter cups, chips, high-fat, high-sugar) were also studied.
• Animals consuming these diets showed memory impairments that lasted even after switching to a healthy diet.

Introduction to GLP-1 Hormones and Drugs [00:02:00]

• Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted from the intestines and also produced in the brainstem.
• Both peripheral and central GLP-1 have appetite-suppressing effects and regulate blood glucose by stimulating insulin secretion.
• Initially developed for diabetes treatment, GLP-1 drugs are now widely known for their weight loss capacity.

  "In its natural form, it's an incretin hormone. So it's secreted from the distal intestines around food ingestion."

GLP-1 Drugs: Superphysiological Levels and Side Effects [00:04:00]

• GLP-1 drugs like Ozempic and Wegovy increase GLP-1 levels thousands of times higher than naturally experienced.
• Clinical trials support their efficacy, but common side effects include nausea and vomiting, leading to discontinuation for some users.
• Mitigating these side effects and ensuring long-term efficacy are key challenges.

Microdosing GLP-1 Drugs [00:05:00]

• Anecdotal reports suggest some people are microdosing GLP-1 drugs to reduce side effects and costs.
• There is currently no scientific data on the efficacy or safety of microdosing GLP-1 drugs.
• The speaker expresses skepticism due to the lack of large clinical trials and the disincentive for pharmaceutical companies to fund such research.

  "I'm not aware of any data on that. Placebos are very effective, so there could be some of that involved."

Non-Weight Loss Benefits of GLP-1 [00:06:00]

• Some individuals, even at healthy body weight, are taking GLP-1 drugs for claimed benefits on cognition and energy.
• The GLP-1 receptor is densely expressed throughout the brain, including regions involved in reward circuitry and the hippocampus.
• This suggests potential applications for substance abuse disorders, memory disorders, and dementia.

GLP-1 Receptor Agonists and Brain Penetration [00:07:00]

• The extent to which GLP-1 drugs cross the blood-brain barrier is a controversial topic.
• Early preclinical evidence suggested brain action, but newer drugs' penetration is less clear.
• Some studies using fluorescent tagging show accumulation in circumventricular organs, while others using radiolabeling suggest some brain entry.

  "The first generation of GLP-1 drugs, so 2005 to 2012, we collected some preclinical evidence in rodents suggesting that a large part of the mechanism of action for food intake suppression was through brain action."

GLP-1's Role in Satiation via the Vagus Nerve [00:10:00]

• GLP-1 likely acts paracrinely on the vagus nerve terminals in the GI tract, signaling satiation to the brainstem.
• This vagal pathway is a major contributor to stopping eating during a meal.
• Selective lesions to the sensory vagus nerve render GLP-1 ineffective in reducing food intake in animal models.

  "So the vagus nerve communicates a lot of within-meal signals that contribute to us stopping eating, right?"

Artificial Sweeteners and Appetite Regulation [00:13:00]

• The effect of artificial sweeteners on appetite and metabolism is controversial, with mixed evidence in humans and preclinical models.
• Preclinical studies suggest that disrupting the link between sweet taste and caloric consequences can perturb appetite and glucose regulation.
• Some animal studies indicate habitual exposure to artificial sweeteners may disrupt sweet taste metabolism and potentially lead to increased appetite and weight gain.

Developmental Exposure to Artificial Sweeteners [00:14:00]

• A study in juvenile-adolescent rodents found that daily consumption of artificial sweeteners (stevia, ACE-K, saccharin) within FDA limits led to adult memory impairments and altered glucose regulation.
• These animals showed larger insulin spikes when glucose was infused and changes in sweet taste receptor expression.

  "And we found that the animals had some memory impairments, which was an unexpected finding."

Memory of Eating Occasions and Subsequent Intake [00:17:00]

• Memories of recent eating occasions can significantly influence how much is eaten at subsequent meals.
• Priming individuals to recall a recent meal led them to consume fewer biscuits in a later taste test.
• Memory of perceived consumption volume, not just actual intake, can affect hunger ratings hours later.

Food Intake's Impact on Memory Systems [00:19:00]

• Mammalian memory systems evolved to promote survival by remembering important events like encountering nutrients.
• Systems traditionally studied for metabolism and appetite also promote memory function, likely to aid in finding and remembering food sources.
• The hippocampus is a key area where satiation systems are tuned into memory systems.

  "We think that these systems that are responding to nutrients when we eat are actually promoting memory function."

Avoiding Dietary Factors That Harm Memory [00:21:00]

• Western diets (high fat, high simple sugar) in adult animals lead to hippocampal-dependent memory impairments.
• The hippocampus appears particularly susceptible to the negative impacts of these diets.
• High sugar consumption during juvenile-adolescent development in rodents can cause long-term memory deficits, potentially linked to the microbiome.

Heat-Treated Foods and Advanced Glycation End Products (AGEs) [00:23:00]

• A study examined the impact of heat-treating otherwise healthy food, inducing the Maillard reaction and creating AGEs.
• Animals consuming an AGE-enriched diet during development showed memory impairments.
• Reintroducing a specific bacterial population eliminated by heat treatment reversed these impairments.

  "And what happens when you heat this food up is there's chemical byproducts of this process. They're called Advanced Glycation End Products."

Memory Impairments and Hippocampal Function [00:25:00]

• Memory tests used include spatial learning in mazes and object recognition tasks, which are hippocampal-dependent.
• In some diet manipulation studies, animals performed at chance levels, indicating a significant memory deficit.

Diet, Metabolism, and Age-Related Dementia [00:27:00]

• Midlife dietary patterns and metabolic status are correlated with increased dementia risk later in life.
• In transgenic Alzheimer's models, a Western diet can exacerbate pathology and accelerate symptom development.
• Maintaining a healthy dietary pattern throughout life is considered more important than switching only when problems arise.

  "There's pretty strong evidence from prospective studies. I mean, they're correlations, but from prospective studies showing that midlife dietary patterns and metabolic status can be associated with an increased risk of dementia later in life."

Exercise and Memory Restoration [00:29:00]

• Exercise has been shown to reverse memory deficits caused by unhealthy diets in rodent models.
• This reversal is partly mediated by changes in the brain, suggesting exercise can counteract some dietary harms.

Gut-Brain Connection and Alzheimer's Pathology [00:31:00]

• Research is exploring the gut's connection to Alzheimer's pathology, including the role of the vagus nerve.
• Lesioning the vagus nerve in animals leads to hippocampal-dependent memory impairments.
• A small study in Taiwan suggested a positive correlation between truncal vagotomy (for stomach ulcers) and developing dementia later on.

  "We've done some work with the vagus nerve. I think I mentioned earlier, and if you lesion the vagus nerve as it's coming out of the gut, the gastrointestinal innervating components of the nerve, animals show hippocampal-dependent memory impairments."

Vagal Nerve Stimulation and Memory [00:33:00]

• Vagal nerve stimulation devices, activated during eating, are being studied for their potential to improve outcomes in a transgenic Alzheimer's rat model.
• These devices have shown promise in rescuing memory impairments caused by unhealthy diets in animals.

Gut Signals to the Hippocampus [00:35:00]

• The hippocampus receives information from the gut via the vagus nerve and circulating hormones like insulin and ghrelin.
• This neural and humoral signaling provides the hippocampus with insight into the body's metabolic state.
• Acetylcholine release in the hippocampus, driven by nutrient sensing and taste, appears crucial for memory formation related to eating occasions.

  "So it's really receiving the neural connection from the vagus nerve but also the humoral sort of longer term energy status connection from these hormones."

The Role of Acetylcholine in Memory and Plasticity [00:37:00]

• Elevated acetylcholine levels in the hippocampus during and after eating are thought to facilitate memory of the experience.
• This system is analogous to how highly palatable foods can hijack reward pathways, but it is also plastic.
• Consuming non-nutritive sweeteners like stevia does not elicit the same hippocampal acetylcholine release pattern.

  "We think that that elevated postprandial level of cetylcholine hippocampus is to allow the animals to remember what what the hell's going on you know like just ate this meal where am i can i get back here and do this again."

Nature of Gut-Brain Signals and Interoceptive Awareness [00:40:00]

• Gut-brain signals are complex, involving various mechanoreceptors and chemoreceptors, and are not a single unified electrical signal.
• The hippocampus processes interoceptive awareness, integrating signals from the gut to inform behavior.
• Individuals with hippocampal damage may detect gut signals but lack the understanding to interpret them appropriately (interoceptive agnosia).

Gut Microbiome and Diet Interactions [00:43:00]

• Early life excessive sugar consumption significantly alters the gut microbiome composition.
• Specific bacterial populations, like Parabacteroides, have been negatively correlated with memory performance in rodents.
• Manipulating these populations (e.g., via antibiotics or enrichment) can impact memory, suggesting a causal link.

  "And in one case we had a population parabacterioides that was elevated in the sugar group i think maybe twofold enough that it was significant and noticeable and it was negatively correlated with memory performance."

The Evolving Field of Microbiome Research [00:45:00]

• The microbiome field is relatively new, with rapid growth in research publications.
• Identifying specific beneficial or detrimental bacteria is complex due to the dynamic and interconnected nature of the microbiome.
• While diversity is often cited, precise answers about individual bacterial roles are still emerging.

Fecal Transplants and Gut Health [00:47:00]

• Fecal microbiota transplantation (FMT) is an FDA-approved treatment for C. difficile infection, demonstrating the power of microbiome manipulation.
• Rebuilding a healthy gut microbiome is a slow process, taking weeks to months, and is influenced by diet, probiotics, sleep, and stress.

GLP-1 Drugs and Potential Micronutrient Deficiencies [00:49:00]

• Concerns exist about potential thiamin and micronutrient deficiencies with long-term GLP-1 drug use, especially in lean individuals not needing weight loss.
• However, most clinical trials are short-term and controlled, and discontinuation rates due to side effects are high.
• The long-term effects of GLP-1 use in diverse populations are not yet fully understood.

The Reinforcement Pathway and Food Choices [00:51:00]

• The mesolimbic dopamine pathway is engaged by palatable foods, substances of abuse, and even bland foods when an individual is in a deprived state.
• Palatable foods tend to activate this pathway more strongly than bland, healthy foods.
• Preferences for foods are plastic and can be recalibrated through dietary changes, potentially making formerly rewarding foods less appealing.

  "Palatable foods tend to tickle that pathway more so than what we consider to be more healthy and and bland foods."

Plasticity of the Reward System [00:53:00]

• Extreme plasticity is seen in conditioned taste aversion, where negative experiences eliminate dopamine responses to previously rewarding tastes.
• While food addiction is debated, the criteria for substance abuse can be argued to apply to certain eating behaviors.
• The comparison to addiction is complex because eating is a necessary behavior.

Processed Food Industry Influence [00:55:00]

• The powerful influence of the processed food and sugar lobbies on public health policy and research is acknowledged.
• Historical instances of industry pushback against studies highlighting the negative impacts of sugar are mentioned.
• A shift in public trust away from large institutions may be influencing the discourse around food and health.

  "I've had a few brushes myself with with the sugar lobby... more of a public facing statements but... when you get press that's when the sugar lobby for lack of a better term may have a forward public statement about that particular study to try and protect them."

Oxytocin's Role in Appetite and Social Eating [00:58:00]

• Oxytocin is known to reduce appetite and food intake, primarily acting on the brainstem to decrease meal size and increase satiation.
• However, recent research suggests oxytocin signaling in the hippocampus may promote food intake in social contexts (social facilitation of eating).
• This highlights the complexity of oxytocin's role, which can vary depending on the brain region and social environment.

  "It's been known for quite some time that that oxytocin can reduce appetite and food intake and through careful studies from harvey grill and others we have identified the brain stem as being the the most robust target of oxytocin signaling to reduce food intake."