Proceedings of the Continuing Nutrition Education Conference 2023: The Impact of Nutrition on Brain Health: From Neurotrophic Factors to Gut–Brain Interactions

Nutrition and Cognitive Health

Karthik V Mahesh

Introduction: Brain health is affected by both modifiable and nonmodifiable factors. Among the modifiable factors, cognitive health is significantly affected by the quality of nutrition. Nutrition is involved in brain development right from the start; for example, fetal brain development is affected by a host of nutritional factors like iodine, iron, zinc, copper, and essential fatty acids. A balanced diet rich in essential nutrients supports brain development and function throughout life. Multiple recent studies and trials show the relative impact of each of these micro/macronutrients on cognitive health.

Interaction between nutrients and cognition:

• Omega-3 fatty acids, vitamins and minerals are vital for neural growth and cognitive abilities. Conversely, diets high in processed foods and sugar can lead to inflammation, potentially contributing to cognitive decline and conditions like Alzheimer’s disease (AD).

• Blood sugar stability is crucial; excessive sugar consumption can lead to insulin resistance, impacting cognitive function. The gut–brain connection highlights the importance of a healthy gut microbiome, influenced by a diet rich in fiber and probiotics, in maintaining mood and cognitive health.

• Omega-3s, found in foods like fish, aid brain cell structure and are linked to better cognitive function. Antioxidant-rich foods, such as berries and nuts, protect brain cells from oxidative stress.

• Hydration is essential, as dehydration can impair cognitive function. A balanced intake of macronutrients (carbs, proteins, fats) provides energy for optimal brain function, with proteins aiding neurotransmitter production.

• The Mediterranean diet, centered on fruits, vegetables, whole grains, fish and olive oil, is associated with better cognitive health. On the flip side, excessive calorie consumption leading to obesity is a risk factor for cognitive decline.

Fats:

• High-fat diet has adverse effects on cognition.¹ Consumption of a high-fat diet stimulates the hippocampus to mount hyperimmune response. There is increased risk of obesity, insulin resistance and diabetes, development of cognitive deficits and AD. Low-fat diets are protective against cognitive decline.

• High saturated fatty acids (SFA) associated with worse cognitive and verbal memory contrasting with monounsaturated fatty acids (MUFA) intake was related to better outcomes.^1,2

• Polyunsaturated fatty acids (PUFAs) regulate the function and structure of neurons, endothelial cells, and glial cells in the brain. They possess antithrombotic as well as anti-inflammatory properties.³

• Eicosapentaenoic acid and DHA; the omega-3 fatty acids; also modify neurotransmission, reduce neuroinflammation, and promote neuronal survival and neurogenesis.

Proteins: In a large meta-analysis, no significant associations were observed between protein intake and global cognition in old age. However, as evident in three studies, there was a positive correlation between memory and protein intake. A cross-sectional study by Li et al. reported a positive association between protein intake from animal foods, meat, eggs, and legumes with cognition.⁴

Carbohydrates: High intake of carbohydrates and low intake of fats and proteins was associated with increased risk of mild cognitive impairment and dementia. Higher carbohydrate content increases vascular risk factors, insulin resistance, diabetes and obesity; it is also an independent risk factors for risk of mild cognitive impairment (MCI)/AD. High-fiber diets play a role in reducing CNS autoinflammation through the gut–brain axis.

Micronutrients:

• Iron: Iron deficiency is associated with poor mental and motor development in infancy and with poor cognition and school achievement during later childhood. Iron deficiency in the brain is associated with disordered neurophysiological mechanisms and, hence, compromise motor and cognitive development.

• Vit-B complex: B vitamins are essential for brain development and function through many mechanisms including neural myelination, brain development, and fetal and child growth. Studies showed association of B-vitamins (niacin, folate, B₆, and B₁₂) with better cognitive function in midlife.

• Vitamin—D, E, K: A systematic review reported that poor outcome in various cognitive tests was linked to a higher dementia incidence risk in patients with low 25(OH)D levels; a cross-sectional United States-based study associated a high vitamin E intake with a higher score on verbal memory, immediate recall, and better language/verbal fluency performance⁵; a cross-sectional study by Chouet et al. on 192 French older adults reported that higher dietary phylloquinone (vitamin K) was associated with better cognition related behavior among older adult.⁶

• Antioxidants: The brain is highly susceptible to oxidative damage, and it has been suggested that oxidative stress or inadequate antioxidant defense might mediate the pathogenesis and progression of dementia. Thus, intake of dietary antioxidants could affect the development of cognitive impairment.

Dietary patterns in cognitive health:

Three promising dietary patterns have been identified with positive affect on brain health, that is, Mediterranean diet, dietary approaches to stop hypertension (DASH) diet, and MIND diet. World Health Organization (WHO) also recommends diet similar to Mediterranean diet

• Containing fruits, vegetables, legumes, nuts and whole grains.

• At least, 400 gm (five portions) of fruits and vegetables daily.

• Less than 10% of total energy intake from free sugars. This is equivalent to 50 gm (or 10 teaspoons).

• Ideally consume <5% of total energy intake (i.e., 25 gm) for additional health benefits.⁷

Conclusion: Omega-3 fatty acids, vitamins and minerals are vital for neural growth and cognitive abilities. Conversely, diets high in processed foods and sugar can lead to inflammation, potentially contributing to cognitive decline and conditions like AD. The gut–brain connection highlights the importance of a healthy gut microbiome, influenced by a diet rich in fiber and probiotics, in maintaining mood and cognitive health. Omega-3s, found in foods like fish, aid brain cell structure and are linked to better cognitive function. Antioxidant-rich foods, such as berries and nuts, protect brain cells from oxidative stress. The Mediterranean diet, centered on fruits, vegetables, whole grains, fish, and olive oil, is associated with better cognitive health. On the flip side, excessive calorie consumption leading to obesity is a risk factor for cognitive decline. In conclusion, a well-rounded diet with diverse nutrients, combined with exercise and adequate sleep, supports cognitive health. Avoiding excessive sugars and processed foods can help maintain mental clarity and function throughout life.

Parkinson’s Disease in Relation to the Gut–Brain Axis: Insights into a Complex Relationship

Sahil Mehta

Introduction: Parkinson’s disease (PD), characterized by symptoms like bradykinesia, tremors and rigidity, alongside a multitude of nonmotor symptoms, is the second most prevalent neurodegenerative disorder. Intriguingly, gastrointestinal disorders such as constipation and delayed gastric emptying can manifest decades before the onset of motor symptoms due to α-synuclein deposition in the neurons of the intestinal submucosa. On various grounds of belief, it is suggested that the gut–brain axis plays a crucial role in the pathogenesis of PD, highlighting the intricate interplay between the gut and the brain. PD is a heterogeneous condition with the pathology of Body first PD or brain first PD. α-synuclein-containing Lewy bodies (LBs) or Lewy neurites need to be identified through histopathological assessments. These LBs are detected in the central, autonomous, and enteric nervous systems.

Body-first PD is characterized by altered microbiota, resulting in lower efficacy of SCFAs production, leading to dysbiosis and leaky gut syndrome (breakdown of intestinal-blood barriers), causing systemic inflammation (release of cytokines), which in turn impairs the blood–brain barrier and is passed to the brain, causing neurodegeneration. Intestinal inflammation caused by bacterial infections might lead to the initiation of α-syn misfolding, and further α-syn pathology propagates retrogradely to the brain via the vagus nerve.^1–5

Review of literature:

• Bifidobacterium, Lactobacillus, and Akkermansia are SCFA-producing microbiota whose increment outside of an “optimal range” is known to aggravate PD. This was evaluated in this study by investigating the relationship between microbiome and PD symptoms.

• A total of 67 patients who suffered from PD and had a positive HP urea breath test were block randomized (1:1) in this placebo-controlled trial. About 32 patients received standard eradication triple therapy and 35 received identically appearing placebo capsules for a span of a week.

• A placebo study with 63 patients who were undergoing treatment with rifaximin was conducted to investigate the contribution of small intestinal bacterial overgrowth (SIBO) in the pathophysiology of motor fluctuations. The patients underwent lactulose, glucose, and urea breath tests for detection of SIBO and Helicobacter pylori infection with reevaluation at 1 and 6 months.

• Out of 280 patients, 72 patients with PD who were eligible, were block randomized (1:1) in a double-blind, placebo-controlled trial. About 34 patients were given multistrain probiotics capsules, while 38 patients were given identical-appearing placebo for 4 weeks with an aim to observe the variation in average number of spontaneous bowel movements (SBM) per week. A comparison was made between the results noted 2 weeks before intervention and during the last 2 weeks of intervention, recorded by daily stool diary.

• A placebo-controlled study with the objective to investigate the efficacy and safety of isosmotic macrogol solution, involving 57 PD patients who were suffering from constipation was conducted over a span of 8 weeks.

Results of the study:

• A variation in SCFAs-producing bacteria in PD patients is responsible for modifying the genetic potential required for SCFAs formation resulting in lower levels of fecal SCFAs in PD patients than controls.

• H. pylori eradication is not accountable for symptomatic improvement in PD patients.

• The occurrence rate of SIBO was found to be higher in patients (in comparison to placebo), while H. pylori infection was not. The relapse rate of SIBO was found to be 43% at 6 months. SIBO eradication resulted in improvement of motor fluctuations without causing changes in the pharmacokinetics of levodopa.

• An improvement was observed in the SBM and stool consistency of the treatment group. When compared to the placebo group, the SBM of treatment group increased by 1.0 ± 1.2 per week.

• Improvement in constipation rating scale, visual assessment scale (VAS) and stools per day was observed with drug compared with placebo.

Conclusion: Both animal and human studies have consistently demonstrated differences in the microbiome of individuals with PD compared to healthy controls. Furthermore, PD-related gastrointestinal disorders can impact the bioavailability of levodopa, a primary medication for managing motor symptoms.

Therapeutic strategies aimed at modulating the gut–brain axis have shown promising results in PD management. These interventions encompass dietary modifications, the use of probiotics, and even fecal microbiota transplantation. Collectively, these approaches offer potential benefits by targeting the intricate relationship between the gut and the brain in individuals with PD. The impact of the gut on PD includes oropharyngeal dysphagia, SIBO, gastroparesis, drooling and delayed gastric emptying (symptomatic in 40% but when investigations done—70–100%).

Vitamin B₁₂ Deficiency and Its Impact on the Peripheral Nervous System

Ritu Shree

Background: Vitamin B₁₂ plays a pivotal role in the metabolic processes of the nervous system, making it one of the most crucial vitamins for proper functioning. When individuals experience vitamin B₁₂ deficiency, it can lead to various neurological manifestations, with myeloneuropathy being the most common presentation, followed by peripheral neuropathy and myelopathy. Additionally, cranial neuropathy can occur, particularly in conjunction with peripheral nervous system involvement.

One distinctive feature of B₁₂ deficiency is its involvement with the optic nerves, which can result in painless bilateral vision impairment. When the peripheral nervous system is affected, it typically leads to a distal, symmetric, and pure sensory polyneuropathy. In more severe cases, motor nerves can also be affected, often accompanied by corticospinal tract and posterior column involvement, a condition referred to as ”subacute combined degeneration of the cord.” However, it is important to realize that nutritional deficiencies often occur together and very rarely in isolation. Therefore, when considering B₁₂ supplementation, it is advisable to also supplement other micronutrients simultaneously.

Diagnosing B₁₂ deficiency involves measuring various biomarkers, including low serum vitamin B₁₂ levels, high serum methylmalonic acid levels, high serum homocysteine levels, and the absence of parietal cell antibodies. Prompt management is essential, and therapeutic supplementation can be administered either orally or parenterally, depending on the severity of the deficiency. It’s important to complement therapeutic supplementation with dietary changes that incorporate vitamin B₁₂-rich foods.

Early detection and intervention are critical in managing vitamin B₁₂ deficiency, as it often leads to dramatic and complete recovery when addressed at an early stage. Therefore, maintaining a high level of clinical suspicion during patient evaluation is crucial for ensuring effective treatment and preventing further neurological complications.¹,²

Case: The patient was a 42-year-old male presented with bilateral diminution of vision for the past 2 months. It was sudden in onset and characterized by simultaneous symmetrical vision loss. No history of pain or headache was reported. Additionally, there was a history of numbness in the feet and fingers for the last 1.5 months, which was symmetric and progressive, associated with paresthesia, and started in the soles ascending upward.

The patient had a past history of hypothyroidism. He consumed a mixed diet and had a chronic alcohol consumption for the past 20 years, along with chronic smoking and tobacco consumption. During the mini–mental state examination, there was a loss of attention noted along with a point lost in recall. However, the vision was 6/60 in the right eye and finger counting was 2 meters in the left eye. There was no relative afferent pupil defect (RAPD). Fundus examination revealed bilateral temporal pallor, with the hue on the lateral part appearing paler than on the medial part. In the motor system examination (lower limb), power and muscle tone were observed to be normal, but there was a loss of deep tendon reflexes in the lower limb, which were preserved in the upper limb. In the sensory examination, joint position sensation and vibration were impaired.

The patient was diagnosed with vision loss and sensory involvement, cerebral neuropathy and bilateral optic neuropathy. Investigations taken into consideration included nutritional deficiency, toxins, demyelination involving optic and peripheral nerve, and genetic causes, as the patient was over 40 years old.¹,²

Results: The optic nerve was found to be normal, but the sheath was slightly prominent. Hyperintensities were observed in the parietooccipital subcortex, which were not contrast-enhancing. Pure sensory axonal neuropathy involving bilateral upper and lower limbs with small fiber involvement was noted. In the general blood workup, cerebrospinal fluid (CSF), vasculitis blood tests, hemoglobin (Hb), liver function tests (LFT) and renal function tests (RFT) were normal. Mean corpuscular volume (MCV) was raised to 105, and thyroid-stimulating hormone (TSH) and antithyroid peroxidase (anti-TPO) antibodies were elevated. Vitamin B₁₂ levels were low at 76.8. The peripheral blood smear showed a macrocytic picture. Antiparietal cell antibody test was performed after the diagnosis of vitamin B₁₂ deficiency, which tested positive. The patient was started on parenteral B₁₂ supplementation for 2 months. Vision improved from 6/60 to 6/9, and finger counting improved to 6/12. Simple B₁₂ supplementation improved vision from nearly blind to almost normal vision with the reversal of optic neuropathy symptoms. Blood tests for predicting the deficiency status include serum methylmalonic acid (serum MMA), which is elevated and has 98% sensitivity; total homocysteine levels, along with serum MMA, are highly sensitive in detecting vitamin B₁₂ deficiency, especially in patients whose serum B₁₂ levels are found to be normal.

Conclusion: Vitamin B₁₂ blood level tests must be performed in every case presenting with vision loss. The treatment involves immediate parenteral therapy. A daily dosage is administered initially for a week, which is further scheduled to thrice a week. Later, a weekly therapy is administered for 4–8 weeks, which is further scheduled to once a month. A lifelong therapy is required if an irreversible cause for deficiency is known, like pernicious anemia. Oral therapy can also be administered in a dose of 1000–2000 µg daily. Initial reticulocytosis resolves over 1–2 weeks. The resolution of anemia takes over 4–8 weeks. If the treatment is started early, there is profound neurological recovery. There is a growing recognition of the influence of nutrition on various neurological disorders. Vitamin B₁₂ deficiency is a treatable, reversible cause of devastating neurological symptoms. It has to be recognized at an early stage having varied clinical manifestations which are not obvious. The deficiency has to be suspected in all the cases. Reliance on clinical symptoms to treat diseases even though test reports are discorded is necessary. Also, undue folic acid supplementation might mask vitamin B₁₂ deficiency.

Role of Nutrition in Optic Nerve Health

Aastha Takkar

Introduction: ”Nutrition” encompasses what to eat and what not to eat, how to eat and when to eat. The optic nerve, often referred to as the ”window” to the inner workings of the brain due to its proximity and functional similarity to white matter, is an essential component of our visual system. Understanding the relationship between nutrition and optic nerve health is crucial for maintaining vision and overall well-being.

One of the leading reversible neurological causes of blindness is idiopathic intracranial hypertension (IIH), a condition that primarily affects young females of reproductive age. IIH is strongly linked to obesity and is often associated with recent weight gain or hormonal therapy. Healthy nutrition plays a pivotal role in the treatment of these patients.¹

The optic nerve is the storehouse of mitochondria, especially in the unmyelinated part of the optic nerve. With the occurrence of mitochondrial disease, the initial effects manifest in the eye. While once believed to be immune-privileged, both the optic nerve and the brain are now recognized as organs prone to inflammation in certain autoimmune conditions like multiple sclerosis (MS).²

Case 1: The patient was a 34-year-old female presented with a headache, blood spots in front of the eyes, and blurring vision. Edema in the fundi was observed along with a dark visual field. The optic nerves were tortuous, which was suggestive of increased intracranial pressure. Increased intracranial pressure could have resulted from hemorrhage, tumor, or infection in the brain. However, in this particular patient, the brain tests were normal. The patient was diagnosed with idiopathic intracranial hypertension, which could be the cause of vision loss. She was advised to lose 6% of body weight over a span of 6 months.

Case 2: The patient was a 48-year-old male presented with a history of sudden onset vision loss when he got up after sleep in the morning. He had a personal history of heavy smoking and alcohol consumption. Methyl alcohol amblyopia was the diagnosis made. Basal ganglia were seen to be hypodense. Both the eyes and brain were damaged due to high alcohol and tobacco consumption. In this case, the optic nerve underwent atrophy overnight.

Case 3: The patient was a 38-year-old male suffering from tuberculosis who was started on ethambutol and presented with vision loss. The patient suffered from optic atrophy associated with ethambutol administration.

Case 4: The patient was a 26-year-old female presented with a headache, pain in eye movement, and diminishing vision. She suffered from mild optic disc edema and was diagnosed with MS. This was the first episode of optic neuritis, with MS being a trigger for inflammation.

Methodology: Treatment protocols include weight loss and mindful eating as a primary intervention. The lost weight has to be maintained for a long period of time.

The treatment protocols for amblyopia are consumption of antioxidants. Early intervention with antioxidant rich diets lowers the severity of amblyopia.

The treatment for most of the deficits of MS involves steroid administration, which are anti-inflammatory agents. Additionally, treatment with probiotics, vitamin D (even in supratherapeutic doses), and low-fat diets is recommended. Statins can also be used as lipid-lowering agents as evidence-based therapy along with the standard treatment for MS.

Results and conclusion: The renowned IIH-Treatment trial even suggested that isolated weight loss can provide substantial benefits, leading to improvements in visual fields, visual acuity, headache scores, and overall quality of life. While medications like decongestants and diuretics can enhance these benefits, nutrition remains a fundamental aspect of holistic patient management. Anti-inflammatory diets, such as Mediterranean, MIND or ketogenic diets, may prove beneficial in managing these conditions. Additionally, measures such as high-dose vitamin D supplementation, probiotics, and statin use have shown promise in the treatment of MS.

The optic nerve’s vulnerability extends to its high concentration of mitochondria in the papillomacular bundle and unmyelinated regions, making it susceptible to systemic, metabolic, and toxic insults. Avoiding oxidative factors such as smoking, alcohol and addictive substances is crucial, and supplementing the diet with antioxidant-rich foods like colorful vegetables and fruits can be of significant importance.

It’s essential to emphasize that it’s not just the quantity of food that matters but also the quality and knowledge of what to eat, when to eat and how to eat. This holistic approach underscores the significance of nutrition in maintaining optic nerve health, contributing to the preservation of vision and overall ocular and neurological well-being.

Case Study: Nutritional Management in Cerebral Palsy and Dystonia

Kamna Bhatti, Kamakshi Kalia

Introduction: Cerebral palsy (CP) is damage to parts of the brain that control body movements and muscle coordination. Patients with CP are vulnerable to nutritional inadequacy, with the leading cause being muscle spasticity, including oromandibular spasm.

These patients often have manifestations like dysphagia, elevated metabolic needs, nutritional malabsorption induced by abnormalities in the gastrointestinal tract, all of which leads to severe malnutrition and depression.^1,2

Case: The patient was a 53-year-old male presented with CP and dystonia coexisting with metabolic encephalopathy and altered gastrointestinal (GI) motility, specifically diarrhea. Impaired nutrition resulted in malnutrition, growth failure, decline in sensorium [Glasgow Coma Scale (GCS)], pressure ulcers (grade III), micronutrient deficiencies, and protein-energy malnutrition (PEM) with a BMI of 14.7 kg/m². Despite growing recognition of nutritional interventions for the treatment of diarrhea, there is limited understanding and evidence, primarily due to small sample sizes and the absence of precise biochemical indicators.

The case study aimed to introduce adequate nutritional support and monitoring as an integral part of care for CP. The patient presented with gastroesophageal reflux disease (GERD), chronic constipation accompanied by diarrhea (watery stools 12×/day) due to diminished anal tone leading to rectal prolapse. Nutritional requirements were increased due to impaired intestinal absorption, pressure ulcer, and high catabolic rate. The patient experienced constipation again due to dystonia.

Methodology: The calorie target was set at 30 kcal/kg ideal body weight (IBW) and protein intake at 1.5–2.0 gm/kg IBW according to ESPEN guidelines. Dyselectrolytemia was managed through specific dietary supplementations. Nutrition rehabilitation was initiated enterally with a peptide-based formula, which was later modified to starch and chicken-based formula feeding. These feeds were titrated throughout weeks in accordance with stool frequency and sensitivity of the gastrointestinal tract and continued for a month to achieve the adequate level of energy and protein content. Probiotic feeds were added to the diet to promote the growth of healthy microbes. Vegetable fibers were incorporated into the diet to treat constipation.

Results: Improved sensorium was noted, with a GCS scale of E4V1M6, indicating increased alertness. There was a noticeable improvement in pessimistic behavioral changes, and the bed sore had healed to grade I. Diarrhea resolved to occurring only once per day, and constipation also resolved. The patient’s BMI improved to 16.7 kg/m².

Conclusion: Nutritional management continues to be the cornerstone of therapy. The study concludes that evidence-based dietary and nutritional interventions improve the quality of life of patients with CP.