You might envision a candlelight dinner, chocolates, and champagne or a get together or hike with a prospective love interest.  Alternatively, you may feel like V-day is just hype to sell a ton of greeting cards and roses and that it kicks other kinds of love out of the way. You may be lonely and longing for connection right now, but whichever of these scenarios you relate to, just remember - loving and being loved are always available. We each have a deep capacity for romantic love, for loving a child, friends, our family and for loving ourselves.
 
Our ability to share love and to receive love depends upon so many things including how we were raised, how we saw those around us demonstrate affection, trauma we might have experienced and our sense of self-worth.
 
“Your task is not to seek for love, but merely to seek and find all the barriers within yourself that you have built against it.”   Rumi

Romantic love.
 
Euphoria, increased energy, hyper-focus on the loved one, and intense emotions are all a part of the experience of ‘falling in love’.  These feelings relate to specific neural activity from chemicals in the brain.
  
When Kenny Rodgers sang “Love is a Drug,” he wasn’t all that far from the truth.
 
Lightning strikes when it hits the ground
Heavy is the head that wears the crown
Wheels are gonna roll, drums gonna pound
Love is a drug that you can't put down
Love is a drug that you can't put down.
 
Have you ever stopped to think about what's really going on in that intricate dance of emotions we call love? Falling in love happens with an irresistible cocktail of hormones and chemicals that result in feelings characterized by exhilaration, intrusive thinking, not being able to eat or sleep, or obsessive thoughts and more.
 
According to a team of scientists led by Dr. Helen Fisher at Rutgers, romantic love can be broken down into three categories: lust, attraction, and attachment. Each category is characterized by its own set of hormones stemming from the brain (Table 1).

​Researchers have scanned the brains of people who are madly in love and found a heavy surge of dopamine, a neurotransmitter in the brain’s reward system that helps people feel pleasure. 
High levels of dopamine and a related hormone, norepinephrine, are released during attraction.  These chemicals make us giddy, energetic, and euphoric, even leading to decreased appetite and insomnia. The initial phase of falling in love and intense infatuation lasts for several months or even years for some.   
 
During the next phase, there is increased intimacy, commitment, and attachment. This is driven by 2 hormones called oxytocin and vasopressin.  Oxytocin helps us feel safe and secure after the initial high cortisol and stress of the uncertainty and risk of falling in love. The more time you spend with your partner, the more oxytocin you produce; the more oxytocin you produce, the more you may desire your partner. Vasopressin promotes behaviors of vigilance and being territorial and self-protective. 
 
And when you fall in love, your serotonin levels go down — which is the same trend typically found in people with obsessive-compulsive behavior. This explains why people in the early stages of love can become obsessed with continuous connection, and sometimes being overly pre-occupied such as wondering where someone is and who they’re with, the obsessing looping and tireless rumination, or the anxiety over them not texting you back.

A physician once said, “The best medicine for humans is love.” Someone asked, “What is it doesn’t work?” He smiled and said, “Increase the dose.”  
 
“The greatest thing you'll ever learn is to love and be loved in return.” 
― Moulin Rouge

The Power of Love ​

In hope, healing, and with love,
Dr. Suzanne Gazda and Dr. Ilene Rusk
 
References:
 
Acevedo, B. P., Aron, A., Fisher, H. E., Brown, L. L. (2012) Neural correlates of long-term intense romantic love. Social Cognitive and Affective Neuroscience, 7, 2, pp. 145–159.
 
Aykutoğlu B, Uysal A. The relationship between intimacy change and passion: A dyadic diary study. Front Psychol. 2017. https://www.frontiersin.org/journals/psychology/articles/10.3389/fpsyg.2017.02257/full
 
Cacciopo, S. Wired for Love: A Neuroscientist's Journey Through Romance, Loss, and the Essence of Human Connection. MacMillan.
https://us.macmillan.com/books/9781250790606/wiredforlove
 
Dryden-Edwards, R., Stoppler, M. C. (2017). The difference between healthy and obsessive love. MedicineNet. https://www.medicinenet.com/confusing_love_with_obsession/views.htm
 
Durayappah-Harrison MAPP, A. Brain Study Reveals Secrets of Staying Madly in Love. Psychology Today. 2011. https://www.psychologytoday.com/intl/blog/thriving101/201102/brain-study-reveals-secrets-staying-madly-in-love
 
Jia H, Lubetkin EI. Life expectancy and active life expectancy by marital status among older U.S. adults: Results from the U.S. Medicare Health Outcome Survey (HOS). SSM Popul Health. 2020;12:100642. Published 2020 Aug 15. doi:10.1016/j.ssmph.2020.100642
 
Salinas J, O’Donnell A, Kojis DJ, et al. Association of Social Support With Brain Volume and Cognition. JAMA Netw Open. 2021;4(8):e2121122. doi:10.1001/jamanetworkopen.2021.21122
 
Wells JL, Haase CM, Rothwell ES, et al. Positivity resonance in long-term married couples: Multimodal characteristics and consequences for health and longevity. J Pers Soc Psychol. 2022;123(5):983-1003. doi:10.1037/pspi0000385

Whether our choices are due to lack of access or lack of time, we far too often turn to convenience foods that are highly processed and contain excess salt, fat, refined sugar and numerous additives. And this Standard American Diet or SAD nutritional approach tends to provide very few vitamins.
 
Even if you try to follow a healthy dietary regimen (i.e., non-GMO, organic or grass-fed and free-range products), there is mounting evidence that many of today’s whole foods simply don’t contain the same levels of vitamins and nutrients as they did 70 years ago. And this reduction in values can over time potentially impact our health.
 
New research shows cognitive benefits with multivitamin supplementation.
 
You may think of multivitamins as being primarily beneficial to overall health. But a new study shows that daily supplements can “significantly boost memory and slow cognitive aging in older adults compared to placebo.”


In the third COcoa Supplement and Multivitamin Outcomes Study (COSMOS), researchers looked at the effects on cognitive health in 573 participants who took a daily multivitamin containing 20+ micronutrients; study methods included close examination of all participants through direct visits. In conjunction with the research, a meta-analysis of more than 5,000 individuals was also conducted across three cognition studies within the trial.

The findings: older adults taking the multivitamin supplement exhibited a statistically significant reduction in memory loss and cognitive aging compared to those on a placebo.

But which multivitamin should you take?
 
Our markets and drugstore shelves are filled with all kinds of supplements – but it’s important to remember the quality among different brands varies widely. Consumers should choose products from companies that provide certifications (ideally third-party) assuring the supplement’s high quality and that it actually contains the ingredients listed on the label.

While our practice recommends multivitamins made by Pure Encapsulation or Thorne, there are many other companies that produce similar high-quality options.
 
(Dr. Gazda’s tip: “If you’re a smoothie fan like I am, I also use Ka’chava in my smoothie that provides most if not all the daily nutrients, plus it is a great protein source!”)
 
And don’t forget Intermittent Fasting!
 
Mark Mattson, a neuroscientist at Johns Hopkins University, has studied intermittent fasting for 25 years and has stated that if we started intermittent fasting (IF) in mid-life, we would dramatically delay the onset of neurodegenerative disease and slow down aging. 
 
Our blog library also includes several related articles about the effects of IF in neurological disorders including:
Intermittent Fasting and Alzheimer’s
https://www.suzannegazdamd.com/blog/intermittent-fasting-could-it-be-instrumental-in-the-fight-against-alzheimers
 
Intermittent Fasting and MS
https://www.suzannegazdamd.com/blog---ms-in-the-news/intermittent-fasting-and-dietary-restriction-for-ms
 
Intermittent Fasting
https://www.suzannegazdamd.com/blog/intermittent-fasting
 
 
And most recently, Dr. Paul Marik, Front Line COVID-19 Critical Care Alliance (FLCCC), and I discussed at length the attributes of IF in relation to brain health; you can view the full webinar at: https://covid19criticalcare.com/intermittent-fasting-and-brain-health-2/
 
 
Additional thoughts: what about COVID and brain health?
 
Following the events of 2020 and ensuing years, it’s very clear that our neurological wellbeing has been greatly impacted. So much so that in 2021, the Alzheimer's Association issued a press release stating, "Cumulative data points to disturbing trends showing COVID-19 infections leading to lasting cognitive impairment and even Alzheimer’s symptoms."
 
A number of studies have shown that after recovering from a mild COVID infection there is a risk of Alzheimer's disease even in younger populations and in some instances, the presentation shows a rapid onset (i.e., within 6-12 months post infection).
 
It’s not only a COVID infection that can compromise our neurological health – in fact, this report from JAMA Neurology on the results of the U.K. Biobank study published in December 2023 revealed 15 risk factors for young-onset dementia, many of which are modifiable:
 
1.         Lower formal education
2.         Lower socioeconomic status
3.         The presence of two apolipoprotein E4 allele
4.         Complete abstinence from alcohol
5.         Alcohol use disorder
6.         Social isolation
7.         Vitamin D deficiency
8.         High levels of C-reactive protein
9.         Reduced handgrip strength
10.       Hearing impairment
11.       Orthostatic hypotension
12.       Stroke
13.       Diabetes
14.       Heart disease
15.       Depression
 
There is no one approach and certainly no single supplement that can combat the effects of a poor diet, prolonged sedentary indoor lifestyle, lack of exercise, or overindulging in alcohol. More than ever, we need to be diligent and educate ourselves about the best ways to optimize brain health now.
 
We’ll discuss further in an upcoming blog some suggested supplements to consider in addition to high-quality multivitamins. But it’s imperative we stay vigilant toward a goal of better wellness and stay curious!
 
In hope and healing,
Dr. Suzanne Gazda
 
 
References:
 
Vyas, C. et al. Effect of multivitamin-mineral supplementation versus placebo on cognitive function: results from the clinic subcohort of the COcoa Supplement and Multivitamin Outcomes Study (COSMOS) randomized clinical trial and meta-analysis of 3 cognitive studies within COSMOS. The American Journal of Clinical Nutrition. 2024.
https://www.sciencedirect.com/science/article/abs/pii/S0002916523663427?via%3Dihub 
 
Healthline. Best vitamin brands for 2024.
https://www.healthline.com/nutrition/best-vitamin-brands#A-quick-look-at-the-best-vitamin-brands
 
Ka’Chava. Your daily superblend.
https://www.kachava.com
 
Baez, K. Biohacking Brain Health: Research Exploring Fasting and Diet Changes Shows Promise in Delaying Alzheimer's Disease, Improving Cognition. Bright Focus Foundation. 2023.
https://www.brightfocus.org/alzheimers/article/biohacking-brain-health-research-exploring-fasting-and-diet-changes-shows-promise
 
Alzheimer’s Association International Conference (AAIC). COVID-19 Associated with Long-Term Cognitive Dysfunction, Acceleration of Alzheimer’s Symptoms. 2021.
https://aaic.alz.org/releases_2021/covid-19-cognitive-impact.asp
 
Wang L, Davis PB, Volkow ND, Berger NA, Kaelber DC, Xu R. Association of COVID-19 with New-Onset Alzheimer's Disease. J Alzheimers Dis. 2022;89(2):411-414. doi:10.3233/JAD-220717
 
Xu, E., Xie, Y. & Al-Aly, Z. Long-term neurologic outcomes of COVID-19. Nat Med 28, 2406–2415 (2022). https://doi.org/10.1038/s41591-022-02001-z
 
Taquet M, Sillett R, Zhu L, et al. Neurological and psychiatric risk trajectories after SARS-CoV-2 infection: an analysis of 2-year retrospective cohort studies including 1 284 437 patients. Lancet Psychiatry. 2022;9(10):815-827. doi:10.1016/S2215-0366(22)00260-7
 
Davis, H.E., McCorkell, L., Vogel, J.M. et al. Long COVID: major findings, mechanisms and recommendations. Nat Rev Microbiol 21, 133–146 (2023). https://doi.org/10.1038/s41579-022-00846-2
 
Hendriks S, Ranson JM, Peetoom K, et al. Risk Factors for Young-Onset Dementia in the UK Biobank. JAMA Neurol. Published online December 26, 2023. doi:10.1001/jamaneurol.2023.4929

But vitamin D deficiencies are hardly a problem unique to this country – it’s also a global concern linked to significant health consequences, including obesity, diabetes, hypertension, and neurodegenerative disorders such as Alzheimer’s.
 
In order to address these deficiencies, we have to look more closely at the underlying reasons such as:

• Our inside-oriented lifestyles, whether we’re working, attending school, or watching television on the weekends. We have essentially become the Indoor Generation!
• Our regular use of sunscreens.
• Tinted windows at home or in vehicles.
• Wearing clothing designed to block the sun that also effectively blocks UVB or ultraviolet B light – even in the summer. UVB radiation is necessary for our body’s synthesis and production of vitamin D.

 
Note that individuals who have more melanin in their skin, are obese, older, or consistently avoid the sun are potentially more at risk of a deficiency in the absence of high-quality supplementation.
 
What about the role of vitamin D in brain health?
 
Vitamin D plays several vital roles in normal brain physiology, including modulating synaptic plasticity.  Synaptic plasticity refers to the ability of neurons to modify the strength of their connections. It is estimated that we have approximately one billion neurons and trillions of synaptic connections, and it is imperative that the lines of communication interact both efficiently and effectively for our neural processes.
  
But a vitamin D deficiency can impact this synaptic plasticity through numerous avenues, including l-type voltage-gated calcium channels and regulation of various neurotransmitters, including nitric oxide. Additionally, vitamin D deficiency appears to render neurons more vulnerable to injury.
 
In 2014, researchers identified more evidence supporting the importance of vitamin D in regulating the release of nerve growth factor (NGF), an essential molecule for the neuronal survival of hippocampal neurons as well as cortical neurons.
 
A very large study recently published in JAMA Neurology again points to the importance of vitamin D for brain health. The UK Biobank research is the most expansive of its kind, analyzing data from over 356,000 people under the age of 65 and identifying 15 lifestyle and health risk factors associated with early-onset dementia. In addition to vitamin D deficiency, other risk factors include high levels of inflammatory C-reactive proteins, specifically in women, orthostatic hypotension (a form of low blood pressure that happens when standing up from sitting or lying down), heart disease, depression, and other potentially modifiable issues.
 
Significant results shown with vitamin D supplementation.
 
Published research in 2023 revealed findings that among those who developed dementia within ten years, about 75 percent were non-supplement takers compared to only 25 percent who regularly took vitamin D supplements. Supplementation provided greater protection for women, though it reduced dementia risk in both sexes, with researchers noting that “vitamin D exposure was associated with significantly longer dementia-free survival and lower dementia incidence rate.”
 
A 2022 investigation included decedents of the Rush Memory and Aging Project (MAP) and measured vitamin D concentrations in four brain regions both ante-mortem and postmortem. Study authors found higher brain 25(OH)D3 concentrations were associated with a 25 to 33 percent lower odds of dementia or mild cognitive impairment (MCI) in subjects at the final visit before death. Low levels of vitamin D are also associated with reduced gray matter, where over 90 percent of our neurons are located, which can fuel cognitive impairment.

What can we do to optimize our brain health?

While regular sun exposure is the most natural way to get our D, the daily demands of life sometimes get in the way! And the amount of time and percentage of exposed skin it takes to get enough vitamin D will vary based on geographics, weather conditions, and even the amount of melanin your skin contains. Generally, we should strive for 10 to 30 minutes of midday sunlight, several times per week; people with darker-skinned complexions may need to spend a little more time than this. But of course, individuals who are fairer-skinned or burn easily will likely have been told to wear sunscreen.  My advice is that we also regularly take a high-quality vitamin D3 supplement ideally with a meal containing some fats to ensure the greatest absorption.
 
Additionally, there are several other supplements to consider as part of a brain health program that we will discuss soon in an upcoming blog. For other related reading, please check out a few of our previous articles:

https://www.suzannegazdamd.com/blog/science-and-history-show-us-just-how-crucial-it-is-for-our-brains-to-get-enough-vitamin-d
 
https://www.suzannegazdamd.com/blog---ms-in-the-news/new-study-finds-vitamin-d-deficiency-linked-to-impaired-cognitive-function-even-in-early-stages-of-ms
 
https://www.suzannegazdamd.com/blog/vitamin-d-deficiency-is-it-another-health-crisis-in-the-making
https://www.suzannegazdamd.com/blog/more-studies-point-to-critical-importance-of-vitamin-d-in-immune-health
 
If you’ve been told you are deficient in vitamin D, there are a number of steps you can take to improve your levels. And as you can see, there are many, many reasons why we all need to be very proactive - our brains and our bodies depend on it! Questions or need to schedule an appointment? Just reach out to our offices and let us know how we can help.
 
In hope and healing,
Dr. Suzanne Gazda
 
References:
 
Holick, M., Chen, T.C. Vitamin D deficiency: a worldwide problem with health consequences.
The American Journal of Clinical Nutrition. 2008. https://www.sciencedirect.com/science/article/pii/S0002916523235935
 
Naeem Z. Vitamin d deficiency- an ignored epidemic. Int J Health Sci (Qassim). 2010;4(1):V-VI.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3068797/
 
Mayne, P., Burne, T. Vitamin D in Synaptic Plasticity, Cognitive Function, and Neuropsychiatric Illness. Trends in Neurosciences. 2019.  https://doi.org/10.1016/j.tins.2019.01.003
 
Anjum I, Jaffery SS, Fayyaz M, Samoo Z, Anjum S. The Role of Vitamin D in Brain Health: A Mini Literature Review. Cureus. 2018;10(7):e2960. Published 2018 Jul 10. doi:10.7759/cureus.2960
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6132681/
 
Gaughran F, Stringer D, Wojewodka G, et al. Effect of Vitamin D Supplementation on Outcomes in People With Early Psychosis: The DFEND Randomized Clinical Trial. JAMA Netw Open. 2021;4(12):e2140858. doi:10.1001/jamanetworkopen.2021.40858. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2787456
 
Hendriks S, Ranson JM, Peetoom K, et al. Risk Factors for Young-Onset Dementia in the UK Biobank. JAMA Neurol. Published online December 26, 2023. doi:10.1001/jamaneurol.2023.4929
 
Ghahremani M, Smith EE, Chen HY, Creese B, Goodarzi Z, Ismail Z. Vitamin D supplementation and incident dementia: Effects of sex, APOE, and baseline cognitive status. Alzheimers Dement (Amst). 2023;15(1):e12404. Published 2023 Mar 1. doi:10.1002/dad2.12404
 
Shea MK, Barger K, Dawson-Hughes B, et al. Brain vitamin D forms, cognitive decline, and neuropathology in community-dwelling older adults. Alzheimers Dement. 2023;19(6):2389-2396. doi:10.1002/alz.12836
 
Raman, R. How to Safely Get Vitamin D From Sunlight. Healthline.com. 2023.
https://www.healthline.com/nutrition/vitamin-d-from-sun#time-of-day

In a world where we are constantly surrounded by overprocessed, empty-nutrient foods, much of the U.S. is losing the “battle of the bulge.” ​

The obesity epidemic is raging with 41.9 percent of all adults that are dealing with the impacts of obesity; adults in Black and Latino communities have the highest obesity rates at 49.9 percent and 45.6 percent respectively.
 
Visceral belly fat accumulates around the abdominal organs deeper within the body and is linked to hypertension, diabetes, insulin resistance, cancer, and poor brain health. A poor diet with high intake of fatty foods and the wrong kind of carbohydrates (which includes refined sugars) and an inactive lifestyle provide the building blocks for an increase in visceral fat.

Your waist circumference is a good indicator of how much fat is deep inside your belly and surrounding your organs:

• For women, 35 inches or more means you’re at risk for health problems stemming from visceral fat. 

For men, the number is 40 inches or more.

Weight gain at midlife predicts more neurological concerns.
 
A preventable risk factor, obesity is associated with greater cognitive decline and increased risk of dementia. And given the present high rates of childhood obesity, it’s critical to recognize and address these risks at the earliest opportunity.
 
High levels of visceral fat have been associated with volume loss in the brain’s hippocampus (the primary memory center of the brain) and other gray matter.  Researchers in a study published in the journal Neurology report that the faster the hippocampal atrophy process, the faster the cognitive decline.
 
Studies have found that people who were obese and had a high waist-to-hip ratio (a measure of belly fat) had on average slightly lower brain volumes compared with people who were a healthy weight. Specifically, belly fat was linked with lower volumes of gray matter, the brain tissue that contains nerve cells.
 
A new study published online in August of this year in the journal Aging and Disease, “Visceral and Subcutaneous Abdominal Fat Predict Brain Volume Loss at Midlife in 10,001 Individuals,” showed that greater visceral and subcutaneous abdominal fat on abdominal magnetic resonance imaging (MRI) scans predicted brain atrophy, especially in women. Study participants included 10,000 healthy adults aged 20-80 years, average age, 52.9 years with 52.8% men and 47.2% women.
 
Researchers investigated the relationship between brain MRI volumes, as well as amyloid and tau uptake, on positron emission tomography (PET) scans, along with body mass index (BMI), obesity, insulin resistance, and abdominal adipose (fatty) tissue in a cognitively normal midlife population. As we’ve previously discussed, amyloid and tau proteins are thought to disrupt communication between brain cells.
 
The volume of subcutaneous fat, or the fat under the skin, and visceral fat were measured using abdominal MRI; brain MRI measured the cortical thickness of brain regions affected by Alzheimer’s disease. PET was used to examine disease pathology in a subset of 32 participants, focusing on amyloid plaques and tau tangles that accumulate in Alzheimer’s disease.
 
The study noted that higher amounts of both visceral and subcutaneous abdominal fat predicted lower total gray and white matter volume, as well as lower volume in the hippocampus, frontal cortex, and temporal, parietal, and occipital lobes.

The researchers also found that a higher visceral to subcutaneous fat ratio was associated with higher amyloid PET tracer uptake in the precuneus cortex, the region known to be affected early by amyloid pathology in Alzheimer’s disease. This relationship was worse in women than men. Additionally, results showed that higher visceral fat measurements are related to an increased burden of inflammation in the brain. Inflammatory secretions of visceral fat, as opposed to potentially protective effects of subcutaneous fat, may lead to inflammation in the brain, one of the main mechanisms contributing to Alzheimer’s disease.

Obesity and “type 3” diabetes.
 
There is solid correlation of obesity to risk of diabetes as well as to diabetes and declining brain health including an increased risk of dementia. Blood sugar dysregulation is intrinsically linked to neurodegeneration. Diabetes and pre-diabetes are linked to insulin resistance.  Insulin resistance harms the brain by impairing neuronal function, altering levels of catecholamines, and promoting neuroinflammation. Catecholamines are the principal neurotransmitters that mediate a variety of the central nervous system functions, such as motor control, cognition, emotion, memory processing, and endocrine modulation.
 
As illustrated in “The Diabetic Brain,” high levels of inflammatory chemicals called cytokines are associated with brain shrinkage and risk of dementia later in life. In recent years, the term “type 3 diabetes” has been used in health media and literature to refer to Alzheimer’s disease, since the neurodegenerative disease is linked to insulin resistance, which is the hallmark of type 2 diabetes, in the brain. Type 2 diabetes, the most common form of the disease, is typically the result of lifestyle factors and genetics.

Tips for getting rid of visceral fat include:

• Eat whole, fresh food, not the packaged, processed goods that have become norm in the Standard American Diet, or SAD. The Paleo diet is an excellent place to start because it has therapeutic benefits in the treatment of diabetes and may help alleviate the elevated blood glucose and insulin resistance that underlie glycotoxic Alzheimer’s disease. Noted functional medicine expert Dr. Jill Carnahan has a helpful guide to check out: https://www.jillcarnahan.com/2013/02/10/a-quick-start-guide-to-paleo-diet/
• Intermittent fasting, a dietary plan where you limit consuming food for a specific period or significantly reduce calories a few times a week. 

Learn more at: https://www.suzannegazdamd.com/blog/intermittent-fasting-could-it-be-instrumental-in-the-fight-against-alzheimers

• Limit added sugar.
• Limit alcohol intake.
• Ideally get at least six hours of sleep per night; note that both too-little and too much sleep has been associated with increased weight.
• Do an aerobic exercise like walking, running, biking, or swimming for at least 30 minutes daily.
• Get more quality, lean protein into your diet. Many studies show that people who eat more protein tend to carry less visceral fat. 
• Reduce stress as much as possible. https://pubmed.ncbi.nlm.nih.gov/11020091/

 
The popularly known adage, “you are what you eat,” continues to be exemplified by the findings discussed here and in many, many other studies. We cannot stress enough the importance of making lifestyle modifications to ideally optimize the wellbeing of our brains and bodies. So, equip yourself with the power of knowledge and learn more about how you can invest in your own healthy future! We encourage you to visit our blog library for additional related reading and, as always, please reach out to our offices if we can help.
 
“You are what you eat - so don’t be fast, cheap, easy, or fake.” 
– Unknown
 
In health and healing,
Dr. Suzanne Gazda
 
References:
 
Trust for America’s Health. State of Obesity 2023: Better Policies for a Healthier America. 2023.
https://www.tfah.org/report-details/state-of-obesity-2023/
 
Crudele L, Piccinin E, Moschetta A. Visceral Adiposity and Cancer: Role in Pathogenesis and Prognosis. Nutrients. 2021;13(6):2101. Published 2021 Jun 19. doi:10.3390/nu13062101
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8234141/
 
Cleveland Clinic. Carbohydrates. 2021.
https://my.clevelandclinic.org/health/articles/15416-carbohydrates
 
Johns Hopkins University and Johns Hopkins Health. The skinny on visceral fat. Retrieved 11/27/2023.
https://www.hopkinsmedicine.org/gim/_documents/Faculty-Resource/The%20Skinny%20on%20Visceral%20Fat.pdf
 
Centers for Disease Control and Prevention. Childhood Obesity Facts. 2022.
https://www.cdc.gov/obesity/data/childhood.html
 
Hanseeuw, B. et al. Association of pathological and volumetric biomarker changes with cognitive decline in clinically normal adults: Harvard Aging Brain Study. Neurology. 2023. https://n.neurology.org/content/early/2023/11/15/WNL.0000000000207962
 
Miller, S. How Your Belly Fat Is Linked to Your Immune System. LiveScience.com. https://www.livescience.com/59405-omentum-belly-fat-immune-system.html
 
Debette S, Beiser A, Hoffmann U, et al. Visceral fat is associated with lower brain volume in healthy middle-aged adults. Ann Neurol. 2010;68(2):136-144. doi:10.1002/ana.22062
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2933649/
 
Ozato N, Saitou S, Yamaguchi T, et al. Association between Visceral Fat and Brain Structural Changes or Cognitive Function. Brain Sci. 2021;11(8):1036. Published 2021 Aug 4. doi:10.3390/brainsci11081036. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8391376/#B4-brainsci-11-01036
 
Raji CA, Meysami S, Hashemi S, et al. Visceral and Subcutaneous Abdominal Fat Predict Brain Volume Loss at Midlife in 10,001 Individuals [published online ahead of print, 2023 Aug 28]. Aging Dis. 2023;10.14336/AD.2023.0820. doi:10.14336/AD.2023.0820
https://pubmed.ncbi.nlm.nih.gov/37728587/
 
Gazda, S. Biomarkers for Alzheimer’s disease. suzannegazdamd.com. 2022.
https://www.suzannegazdamd.com/blog---long-covid/biomarkers-for-alzheimers-disease-a-revolutionary-tool
Kobayashi K. Role of catecholamine signaling in brain and nervous system functions: new insights from mouse molecular genetic study. J Investig Dermatol Symp Proc. 2001;6(1):115-121. doi:10.1046/j.0022-202x.2001.00011.x https://pubmed.ncbi.nlm.nih.gov/11764279/
 
 
Alzheimer’s Association. Diabetes and Cognitive Decline. alz.org. 2023.
https://www.alz.org/media/documents/alzheimers-dementia-diabetes-cognitive-decline-ts.pdf
Bittman, M. Is Alzheimer’s type 3 diabetes? The New York Times. 2012. https://archive.nytimes.com/opinionator.blogs.nytimes.com/2012/09/25/bittman-is-alzheimers-type-3-diabetes/
 
Sanchez, R. The Diabetic Brain in Alzheimer’s Disease. 2019.
https://www.amazon.com/Diabetic-Brain-Alzheimers-Disease-Resistance/dp/1732668701
 
Higuera, V. Diabetes insulin resistance. Everyday Health. 2019.
https://www.everydayhealth.com/type-2-diabetes/insulin-resistance-causes-symptoms-diagnosis-consequences/
 
Stanhope KL, Havel PJ. Endocrine and metabolic effects of consuming beverages sweetened with fructose, glucose, sucrose, or high-fructose corn syrup. Am J Clin Nutr. 2008;88(6):1733S-1737S. doi:10.3945/ajcn.2008.25825D. https://pubmed.ncbi.nlm.nih.gov/19064538/
 
Gazda, S. Sugar and the not-so-sweet news when it comes to our wellbeing. 2023. suzannegazdamd.com. https://www.suzannegazdamd.com/blog/sugar-and-the-not-so-sweet-news-when-it-comes-to-our-wellbeing
 
Dorn, J. et al. Journal of Nutrition. 2003.
https://jn.nutrition.org/article/S0022-3166(22)16028-1/fulltext
 
Hairston KG, Bryer-Ash M, Norris JM, Haffner S, Bowden DW, Wagenknecht LE. Sleep duration and five-year abdominal fat accumulation in a minority cohort: the IRAS family study. Sleep. 2010;33(3):289-295. doi:10.1093/sleep/33.3.289. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2831422/
 
Baby, D. Top exercises for belly fat. WebMD.com. 2023.
https://www.webmd.com/fitness-exercise/top-exercises-belly-fat
 
Loenneke, J.P., Wilson, J.M., Manninen, A.H. et al. Quality protein intake is inversely related with abdominal fat. Nutr Metab (Lond) 9, 5 (2012). https://doi.org/10.1186/1743-7075-9-5.https://nutritionandmetabolism.biomedcentral.com/articles/10.1186/1743-7075-9-5#citeas
 
Epel ES, McEwen B, Seeman T, et al. Stress and body shape: stress-induced cortisol secretion is consistently greater among women with central fat. Psychosom Med. 2000;62(5):623-632. doi:10.1097/00006842-200009000-00005. https://pubmed.ncbi.nlm.nih.gov/11020091/

Certainly, we know that sugar is linked to increased levels of inflammation, which is at the root of virtually every disease including neurological and other conditions like diabetes. And now there is additional research that points to a link between increased sugar consumption and an increase in certain cancers.
 
In this study (“Simple sugar intake and cancer incidence, cancer mortality and all-cause mortality: A cohort study from the PREDIMED trial”) published in Clinical Nutrition in 2021 and involving over 7,000 participants, scientists found that for every additional five grams of sugar consumed in liquid form per day, the incidence of cancer increased by 8 percent. People with the highest sugar intake experienced a 46 percent increase.
 
Just for perspective, one teaspoon of sugar is equal to four grams – so, you can see that it doesn’t take a lot to potentially increase our risk of disease. And many of us are consuming far more than a teaspoon a day – that single can of soda you may have had with your lunch contains roughly 35 to 40 grams of sugar! Multiply that by seven days a week and you can see how it all adds up to unhealthy amounts and greater risks, especially if you are drinking more than one can a day.
 
Another study with over 35,000 participants revealed that people who consumed sugar-sweetened soft drinks more than once per day had an 18 percent increased risk of developing obesity-related cancers than those who rarely consumed such drinks.
 
Other studies have shown those who consumed the most sugar had a 17 percent increased cancer risk compared to those with the lowest sugar intake. This elevated risk was particularly notable for breast cancer, with a 51 percent increase.
 
Your brain on sugar.
 
Back in 2020 we wrote about the impact in particular regarding childhood obesity and incidence of multiple sclerosis. Research led by Queen Mary University of London, U.K. estimates that childhood and adolescent obesity is projected to contribute up to 14 percent of overall risk of multiple sclerosis (MS) by the year 2035.
 
The negative impacts of sugar on our brain function including cognition and memory have also been well documented. Sugar and its various forms (e.g. high fructose corn syrup, dextrose, and glucose) are often ingredients in many of the “comfort foods” we often choose in times of stress. Contrary to improving our mood, excessive sugar consumption may even worsen anxiety, and feelings of sadness.
 
We also know that the subsequent increase in inflammation can disrupt the health of our gut microbiome which in turn can negatively affect the health of our brain. Several articles in our blog library have looked at this gut-brain connection especially in MS patients – but we can all stand to benefit from choosing a healthy diet that ideally limits refined carbohydrates and items with empty calories and focuses on whole, fresh foods. We recommend an autoimmune paleo diet that includes non-GMO products and grass-fed meat and free-range chicken.  And while for some healthy people an occasional cookie or slice of cake may be okay, for most patients in our practice we ask that they eliminate ALL processed foods.
 
It’s important to note that an autoimmune protocol diet (AIP) is not about weight loss; rather, it is intended as a healing approach to wellness.  
 
Understandably, the holidays are a challenge! But you can definitely overcome the hurdles before venturing out to parties and family gatherings with just a few simple strategies – check out https://aiprecipecollection.com/social-life/and be sure to look at their recipes and other resources too.
 
You’ll also find a wealth of additional information in the references below and we encourage you to browse the related reading in our blog library on our website to learn even more. Questions or need to schedule a visit? Just reach out to our offices and we’ll be glad to help!
 
In health and wellness,
Dr. Suzanne Gazda
 
References:
 
Harvard School of Public Health – Adult Obesity
https://www.hsph.harvard.edu/obesity-prevention-source/obesity-trends-original/obesity-rates-worldwide/#References
 
Harvard School of Public Health – Child Obesity
https://www.hsph.harvard.edu/obesity-prevention-source/obesity-trends-original/global-obesity-trends-in-children/
 
Laguna, J. et al. Simple sugar intake and cancer incidence, cancer mortality and all-cause mortality: A cohort study from the PREDIMED trial. Clinical Nutrition. 2021.
https://www.clinicalnutritionjournal.com/article/S0261-5614(21)00367-8/fulltext
 
Hodge, A., Bassett, J., Milne, R., English, D., & Giles, G. (2018). Consumption of sugar-sweetened and artificially sweetened soft drinks and risk of obesity-related cancers. Public Health Nutrition, 21(9), 1618-1626. doi:10.1017/S1368980017002555
https://www.cambridge.org/core/journals/public-health-nutrition/article/consumption-of-sugarsweetened-and-artificially-sweetened-soft-drinks-and-risk-of-obesityrelated-cancers/14DB5E8634853560209984B07CED68B1
 
Debras, C. et al. Total and added sugar intakes, sugar types, and cancer risk: results from the prospective NutriNet-Santé cohort. American Journal of Clinical Nutrition. 2020.
https://www.sciencedirect.com/science/article/pii/S0002916522008978
 
Fuhrman, J. How sugar affects the brain. verywellmind.com. 2022.
https://www.verywellmind.com/how-sugar-affects-the-brain-4065218
 
Gazda, S. Childhood obesity linked to higher risk of MS. suzannegazdamd.com. 2020.
https://www.suzannegazdamd.com/blog/childhood-obesity-linked-to-higher-risk-of-ms
 
Gazda, S. Probiotics, Parkinson’s, and the gut-brain connection. suzannegazdamd.com. 2021.
https://www.suzannegazdamd.com/blog/probiotics-parkinsons-and-the-gut-brain-connection
 
Gazda, S. What does gut health have to do with MS? suzannegazdamd.com. 2023.
https://www.suzannegazdamd.com/blog---ms-in-the-news/what-does-gut-health-have-to-do-with-ms-research-shows-it-could-be-significant
 
AIP Recipe Collection – a guide for your autoimmune healing journey.
https://aiprecipecollection.com/

And it’s not easy to include vitamin D-containing foods in even the healthiest and most varied diets.
 
But it’s vital to understand and recognize just how important this nutrient is to our neurological wellbeing. Every day, we see more and more research that attests to its impact on brain health, including a recent study that showed the association of lower serum 25-OH vitamin D with cognitive impairment and disability in multiple sclerosis (MS).
 
Before your body can utilize it, vitamin D must go through several processes. The first process occurs in the liver where your body converts vitamin D to a chemical known as 25-hydroxyvitamin D (also called calcidiol). The 25-hydroxy vitamin D test is the best way to monitor vitamin D levels; this test is also known as the 25-OH vitamin D test.
 
Low levels of vitamin have been correlated with not only a risk of MS as well as disease progression, but implicated in other neurodegenerative diseases too. Another study from Australia identified that low sun exposure and commensurate low vitamin D status is associated with an increased risk factor for developing pediatric-onset multiple sclerosis. 
 
Research has shown that vitamin D can mediate neurotrophic and neuroprotective mechanisms of the central nervous system, and its deficiency is associated with worse cognitive performance in older adults. Higher vitamin D levels maintain immune homeostasis, and serve to predict neurofilaments, thus indicating less neuroaxonal loss. Homeostasis is the state of steady internal processes and essentially describes what is optimal functioning for our systems, and getting enough vitamin D can be a positive influence toward ensuring this “balance.”
  
Cumulative evidence also indicates that vitamin D can ameliorate neurodegeneration by regulating pertinent molecules and signaling pathways including maintaining Ca2+ homeostasis, reducing oxidative stress, inhibiting inflammation, suppressing the formation and aggregation of the pathogenic protein, and more. We’ve previously written (many times!) about inflammation being at the core of nearly every disease, including neurological conditions, and the impact of increased oxidative stress – so it just makes sense to do everything we can to reduce our risks!
 
Vitamin D deficiency is a universal problem, but it is a modifiable risk factor that we can address for our brain and overall health. In addition to the references we’ve included below, there are many related articles in our blog library so please stop by there for additional reading. Stay curious and stay well!
 
 
In hope and healing,
Dr. Suzanne Gazda
 
 
 
 
References: 
 
Gazda, S. Study finds vitamin D deficiency linked to impaired cognitive function in early stages of MS. suzannegazdamd.com. 2021.
https://www.suzannegazdamd.com/blog---ms-in-the-news/new-study-finds-vitamin-d-deficiency-linked-to-impaired-cognitive-function-even-in-early-stages-of-ms
 
Gazda, S. The indoor generation is missing out on vitamin D. suzannegazdamd.com. 2021.
https://www.suzannegazdamd.com/blog/the-indoor-generation-is-missing-out-on-vitamin-d
 
Gazda, S. Vitamin D deficiency – is it another health crisis in the making? suzannegazdamd.com. 2020. https://www.suzannegazdamd.com/blog/vitamin-d-deficiency-is-it-another-health-crisis-in-the-making
 
Spezia, A.L. et al. Low serum 25‑hydroxy-vitamin D levels are associated with cognitive impairment in multiple sclerosis. Multiple Sclerosis and Related Disorders. 2023.
https://www.sciencedirect.com/science/article/pii/S221103482300545X
 
Sullivan, D. 25-Hydroxy Vitamin D Test. Healthline. 2023.
https://www.healthline.com/health/25-hydroxy-vitamin-d-test
 
Gazda, S. Vitamin D deficiency linked to neurodegenerative disease. suzannegazdamd.com. 2021. https://www.suzannegazdamd.com/blog/vitamin-d-deficiency-linked-to-neurodegenerative-disease
 
Sebastian, P. Association Between Time Spent Outdoors and Risk of Multiple Sclerosis. Neurology. 2022. https://n.neurology.org/content/98/3/e267
 
Annweiler C, Dursun E, Féron F, et al. 'Vitamin D and cognition in older adults': updated international recommendations. J Intern Med. 2015;277(1):45-57. doi:10.1111/joim.12279
https://pubmed.ncbi.nlm.nih.gov/24995480/
 
Tera, J. et al. Vitamin D deficiency is associated with accelerated brain aging in the general population. Psychiatry Research & Neuroimaging. 2022.

Shea, M. et al. Brain vitamin D forms, cognitive decline, and neuropathology in community-dwelling older adults. The J of Alzheimer’s. Dec 2022.

Ghahremani M et al. Vitamin D supplementation and incident dementia: Effects of sex, APOE, and baseline cognitive status. Alzheimer’s and Dementia: Diagnosis, Assessment & Disease Monitoring. March 2023.
 
Wang, W. et al. Vitamin D and neurodegenerative diseases. Heliyon. 2023. https://pubmed.ncbi.nlm.nih.gov/36820164/
​

Intermittent fasting describes a dietary program where you avoid consuming food for a window of time or significantly restrict calories a few times per week. This allows your body to release energy that is stored as fat and may:
 

• Increase insulin sensitivity to help your body utilize this hormone more effectively.
• Encourage weight loss.
• Decrease appetite.
• Improve gut health.
• Help stimulate cell “clean-up” (autophagy) to remove damaged elements from cells.
• Increase brain hormones like brain-derived neurotrophic factor (BDNF).
• Reduce inflammation which can help improve cognitive function.

 
So, what does the research tell us? This latest study was conducted in mice that were fed on a time-restricted schedule and involved the use of intermittent fasting practices to modulate circadian rhythms. The internal circadian timekeeping system modulates cognition and affective function by projections from the master circadian clock. Understanding the basic principles of circadian and wakefulness-sleep physiology can help to recognize how the circadian system modulates human cognition and influences learning, memory, and emotion.
 
In “Circadian modulation by time-restricted feeding rescues brain pathology and improves memory in mouse models of Alzheimer’s disease,” scientists sought to show that by disrupting circadian rhythms or the biological timing processes, it might be possible to better manage Alzheimer’s symptoms. Previously, it was thought that the circadian disruptions noted in Alzheimer’s patients were caused by neurodegeneration – but now, it appears that neurodegeneration may in fact be caused by these disruptions to our biological clock.
 
Some of the study details noted:
 

• Employing” time-restricted feeding without caloric restriction improved key disease components including behavioral timing, disease pathology, hippocampal transcription, and memory in two transgenic models of AD.” 
• The mice subjects exhibited better memory and decreased amyloid protein accumulation.
• Comparable fasting periods for humans (roughly 14 hours/day) demonstrated similar results.
• The scientific team concluded that intermittent fasting could be a significant tool in AD protocols to reduce the inflammation we know is at the root of virtually every disease.
• Researchers believe circadian disruptions could be primary drivers of Alzheimer’s pathology, emphasizing the importance of maintaining a stable internal clock.

And still more research….
 
There are numerous studies that offer similar testaments to the potential power of intermittent fasting in brain health and even immune health.

Citing decreased inflammation, improved vascular health, decreased amyloid accumulations, a research team statedthat “intermittent fasting over the years will potentially reverse or delay the pathological process in Alzheimer’s disease.”
 
Another investigation looked at the association between vascular dementia and dietary regulation, finding that intermittent fasting could lead to better control of energy metabolism, improvements in brain insulin resistance, and suppressed neuroinflammation.
 
A recent study in Nature Aging highlights intermittent fasting as a potential way to decrease the progression of Alzheimer’s disease in mice through changes to the gut microbiota.
 
Exploring the role of intermittent fasting on brain metabolism relevant to neurodegeneration that can occur in obesity and diabetes diagnoses, scientists published their promising results last year and urged for further research to explore this important area.
 
As we continually emphasize, the role of nutritional approaches and dietary considerations must be a key element in any treatment protocol. The foods we eat, and how we consume these, can clearly affect the quality of our cognitive function and many of our body’s processes, even in the absence of a known disorder. 
 
We encourage you to learn more about intermittent fasting and whether this type of approach is appropriate for your health today and tomorrow.  And please let us know if you have questions or need to schedule a visit – we are here to help!
 
Please visit the blog library on our website and use the search function on each page to find additional related reading: https://www.suzannegazdamd.com/
 
In health and healing,
Dr. Suzanne Gazda
 
References:
 
Desplat, P. et al. Circadian modulation by time-restricted feeding rescues brain pathology and improves memory in mouse models of Alzheimer’s disease. Cell Metabolism. (2023). https://www.sciencedirect.com/science/article/pii/S1550413123002735
 
Gazda, S. Intermittent Fasting. SuzanneGazdaMD.com. (2019). https://www.suzannegazdamd.com/blog/intermittent-fasting
 
Wright KP, Lowry CA, Lebourgeois MK. Circadian and wakefulness-sleep modulation of cognition in humans. Front Mol Neurosci. 2012;5:50. Published 2012 Apr 18. doi:10.3389/fnmol.2012.00050

It’s important to know that the body cannot manufacture NAC nor is it found in foods. Like cysteine, NAC bonds with glutamine and glycine to form glutathione, a powerful antioxidant, and aids in regulating glutamate. The most important N-acetyl cysteine mechanisms of action are its antioxidant and anti-inflammatory effects.
 
FDA-approved, NAC is commonly used in treating the side effects of acetaminophen poisoning. Taken in large doses, acetaminophen can cause damage to the liver. As a powerful antioxidant, NAC can lower both oxidative stress and inflammation.
 
Now, numerous studies are pointing to the potential benefits of using NAC to combat the negative impacts of certain chemical imbalances that can occur in our system and lead to the development of some neurological disorders. 
 
So, why is NAC something you should know more about? Keep reading for details about the research and how this amino acid may play a critical role in brain health!
 
NAC for neurodegenerative disease.
 
There are many reasons why NAC can be helpful in neurodegenerative disease. In addition to being a tool to fight oxidative stress and inflammation, NAC easily crosses the blood-brain barrier (BBB), promotes neurogenesis, has neuroprotective properties, regulates glutamate which is an excitatory neurotransmitter, and increases glutathione levels in the body and brain.
 
Note: Glutamate plays a major role in learning and memory. For your brain to function properly, glutamate needs to be present in the right concentration in the right places at the right time. Too much glutamate is associated with diagnoses such as Parkinson's disease, Alzheimer's disease (AD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and Huntington's disease.
 
 
Understanding the role of oxidative stress in neurodegenerative disease.
 
Oxidative stress can occur when there is an imbalance of free radicals and antioxidants in the body. We can think of it much like the accumulation of rust on a car. With years of wear and tear, rust can slowly begin to build unnoticed. But eventually, rust and its subsequent damage can overtake the entire structure. In this same way, unabated oxidative stress can impact our overall health and our brain’s wellbeing.
 
During normal metabolic processes, the body’s cells produce free radicals, which are very unstable molecules; cells also produce antioxidants that neutralize these free radicals. In general, the body can maintain a balance between antioxidants and free radicals. However, free radicals can build up in cells and cause damage to other molecules such as DNA, lipids, and proteins, etc., which can lead to aging and chronic disease including neurodegenerative disease and cancer.
 
What are the risk factors for oxidative stress?
 
Factors that may increase a person’s risk of long-term oxidative stress include:

• obesity
• diets high in fat, sugar, and processed foods
• exposure to radiation
• smoking cigarettes or other tobacco products
• alcohol consumption
• certain medications
• pollution
• exposure to pesticides or industrial chemicals
• exposure to EMF 
• spike protein

 
Oxidative stress and the brain.
 
Because its cells require a substantial amount of oxygen, our brain is particularly vulnerable to the effects of oxidative stress. In fact, according to a 2018 review, the brain alone uses 20 percent of the total amount of oxygen the body needs to fuel itself and all of its processes.
 
Brain cells utilize oxygen to perform intense metabolic activities that subsequently generate free radicals. These free radicals help support brain cell growth, neuroplasticity, and cognitive functioning. But in the presence of oxidative stress, excess free radicals can damage structures inside brain cells and even cause cell death, which may increase the risk of neurodegenerative disease.
 
Oxidative stress also alters essential proteins, such as amyloid-beta peptides, and may modify these peptides in way that contributes to the accumulation of amyloid plaques in the brain.
It also reduces central nervous system (CNS) levels of glutathione, the major free radical scavenger in the brain and this sets up a dangerous situation for the CNS - remember the analogy of a rusty car we mentioned earlier? We know that the CNS is especially vulnerable to oxidative insult due to the high rate of 02 utilization – and the result is neurotoxicity.

Glutathione regulates aging and neurodegeneration.
 
Glutathione is an antioxidant found naturally occurring in the body.  Also known as GSH, it is produced by the liver and nerve cells in the CNS and is made up of three amino acids: glycine, L-cysteine, and L-glutamate. Glutathione can help metabolize toxins, break down free radicals, support immune function, and more.
 
In the brain, glutathione plays a critical role in the antioxidant defense system and the maintenance of redox homeostasis in neurons. Additionally, it serves many pivotal functions in the CNS including the modulation of cellular differentiation and proliferation, apoptosis, enzyme activation, metal transport in cells, and neurotransmission. GSH is also integrally involved in neuronal defense against damage from reactive oxidative species (ROS) associated with aging. ROS is a type of unstable molecule that contains oxygen and that easily reacts with other molecules in a cell.

But as we age, our brain levels of glutathione decrease – and studies have identified GSH depletion in the brain to be commonly found in patients with neurodegenerative diseases such as Alzheimer’s, MS, and Parkinson’s. Scientific evidence confirms that a low level of glutathione can even impair short-term and long-term mechanisms of synaptic plasticity, the process by which our brain adjusts how neurons interact and process information.
 
Boosting glutathione levels in the brain.
 
It’s important to note that there are ongoing differences of opinion as to whether GSH given orally or intravenously can cross the BBB. According to this source, GSH can “hardly cross the BBB, so that brain concentrations cannot be increased by peripheral administration of GSH.” 
 
On the other hand, NAC is readily taken up by neurons and it can help to boost neuronal glutathione levels as it can cross the BBB. And it has been shown to be truly safe and effective, even at relatively high doses.
 
Oxidative stress in Parkinson’s - can NAC help?
 
Parkinson's disease is caused by a loss of nerve cells or neurons in part of the brain called the substantia nigra, located just above the brainstem. Symptoms of the disorder may include muscular rigidity, bradykinesia, tremors in resting limbs, and problems with postural balance.

The importance of oxidative stress in Parkinson’s disease (PD) cannot be overstated and evidence suggests that reactive oxygen species (ROS) are derived from dopamine itself.  One of the reasons for the high levels of oxidative stress is because glutathione, an important antioxidant in the neurons, has been found to be depleted in the brain of PD patients and the magnitude of glutathione depletion appears to parallel the severity of the disease.
 
Studies carried out on cultured human cortical neurons have highlighted that NAC may protect against the programmed cell death (PCD) induced by dopamine and in synaptic mitochondrial preparations in aged mice. If cells are no longer needed, they essentially self-destruct by activating an intracellular death program; in Parkinson’s disease, dopamine neurons in the substantia nigra of human brain are selectively vulnerable.
 
Mitochondrial dysfunction plays a major role in the pathogenesis of PD, but studies have found NAC can also reduce this negative action by inhibiting oxidative stress. Different pathways contribute to the substantia nigra pars compacta (SNPC) neurons vulnerability to oxidative damage including (a) high susceptibility of DA auto-oxidation, (b) reduced antioxidant activity such as glutathione, and (c) increased iron concentration d) deficits in mitochondrial complex I of the respiratory chain.

The post treatment DaTscan showed a ‘substantial increase in dopamine transporter binding in the basal ganglia.  Dopamine transporter is a protein that works to recycle dopamine after its release in the brain. In Parkinson’s, dopamine transporter levels may be reduced to up to 70%. But this study showed that NAC increased this protein, thereby making more dopamine available.  The UPDRS score in the NAC treated group was improved from baseline.
Diagram Credit:  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0157602

In a 2019 investigation, forty-two patients with PD were randomized to either weekly intravenous infusions of NAC (50 mg/kg) plus oral doses (500 mg twice per day) for 3 months or standard of care only. Participants received pre- and post-NAC administration brain imaging studies using ioflupane (DaTscan) to measure dopamine transporter (DAT) binding. In the NAC group, significantly increased DAT binding was found in the caudate and putamen compared with controls along with significantly improved PD symptoms as seen in this diagram. 

In these images, the ones on the right are post NAC.

The results suggest once again that NAC may positively affect the dopaminergic system in patients with PD, with corresponding positive clinical effects.
 
What about NAC in MS?
 
Scientific evidence has found that oxidative stress plays a major role in the pathogenesis of multiple sclerosis (MS). The results of this study suggest that NAC administration alters resting CBF (cerebral blood flow) in MS patients, and this is associated with qualitative improvements in cognition and attention. The experimental group received NAC intravenously (50 mg/kg) once per week and orally (500mg 2x/day) the other six days.  The study lasted 2 months. 

Additional efforts focused on MS research relevant to the use of NAC include:
 

• An exploratory research trial also noted improvements in brain metabolism in patients with MS, particularly in areas that support cognition such as the frontal and temporal lobes in patients with multiple sclerosis. In addition, patients reported qualitative improvements in their cognitive and attention focusing abilities.

 
The dose given was 50 mg/kg mixed into 200 ml of D5W infused over ~1 h 1x per week. Subjects additionally took 500 mg NAC tablets twice daily on the days that they did not receive the intravenous form of NAC.  The study continued X 2 months. 
 

• An ongoing study is continuing to look at the efficacy of orally administered NAC as a potential neuroprotectant agent in progressive forms of MS.   The dose being studied is 1200 mg three times a day along with the patients current DMT (disease modifying therapy)

 

• In yet another study, NAC was shown to be more effective than amantadine in helping MS fatigue.

 

• Reduced levels of anxiety were seen in this study using oral NAC in MS patient.

 
It is important to remember that the body requires both free radicals AND antioxidants – an imbalance that results in too many or too few of either may lead to health problems.
 
KEY TAKEAWAYS:
 

• NAC may contribute to neurological health.
• We cannot obtain NAC directly from food sources.
• NAC can inhibit damaging oxidative stress.
• Studies show NAC could reduce mitochondrial dysfunction.
• NAC may boost levels of glutathione, an important antioxidant and free radical scavenger.
• No single drug or supplement can compensate for other risk factors, including poor lifestyle choices.

 
Optimizing our neurological wellbeing.
 
If you’re a regular reader of our blogs, you know that we often emphasize the importance of following a healthy lifestyle as the first important step in promoting brain health. 
 
As this blog has noted, reducing oxidative stress is key to also reducing harmful inflammation and the resulting problems that can arise from it. And as we’ve also frequently discussed, there is a direct link between the state of our gut and the health of our brain!  Dr. Terry Wahls, who following her MS diagnosis from over 20 years ago designed and adhered to a unique protocol that includes dietary controls, recently wrote about the benefits of intermittent fasting and caloric restriction as a tool for disease management.
 
Our recommendations always start with choosing a healthy nutritional approach based on whole foods over processed, adequate proteins, plenty of vegetables and some low sugar fruits, complex carbohydrates over refined products, and minimal sugary treats. Always opt for healthy fats like olive oil, the heart of the Mediterranean diet. It is especially important to choose, when possible, non-GMO foods and sustainably raised produce and meat.
 
Inset: You don’t have to totally deprive yourself of something sweet! If you too are a chocolate lover, there are ways to satisfy that craving in moderation that also could benefit your brain: https://www.suzannegazdamd.com/blog/listen-to-your-brain-and-go-ahead-and-eat-the-chocolate
 
We are what – and when – we eat.
 
We’ve recently discussed in another blog how the state of our gut health and microbiome could play a big role in the prognosis of autoimmune neurological disease including multiple sclerosis.  As such, we often recommend intermittent fasting to optimize brain health. In this trial, just one of many investigations, MS patients that used intermittent caloric restriction over a period of 12 weeks showed therapeutic effects with a marked increase in brain volume measurement as determined by MRIs, as well as improved blood flow and reduction in neuroinflammation. 
 
Restricting the hours when you eat has been shown as well to significantly improve memory, according to a study in the Journal of the Academy of Nutrition and Dietetics. In this study, after 4 weeks of intermittent fasting, performance on a spatial planning and working memory task and on a working memory capacity test increased significantly. Additional research on animals has found that intermittent fasting improves learning and memory.
 
As we continually emphasize, it’s best to stick to an anti-inflammatory diet that includes a variety of healthy, whole foods. Additionally, we should:
 

• Exercise regularly.
• Practice stress reducing techniques like meditation.
• Did we mention getting enough sleep, like 7 to 8 hours nightly? 
• Reduce or eliminate exposure to toxins and chemicals, whether environmentally occurring or by quitting smoking.
• Work toward achieving a healthy weight; obesity has been linked to increased levels of oxidative stress and excess fat cells produce inflammatory substances that can elevate both inflammatory activity and the production of free radicals.

 
High levels of oxidative stress are implicated in aging and neurodegenerative disease. But utilizing proven measures to address factors that can fuel excess oxidative stress and employing antioxidant therapies may offer significant health benefits. Indeed, in restoring cellular glutathione, a key antioxidant that decreases with age and in neurodegenerative disease, it’s possible that NAC may be an especially important option.
 
It really is so important that each of us commits to being an informed and active participant in our own health goals! As part of this process, it’s crucial to learn as much as we can about the ways that food and other lifestyle influences can affect our wellbeing. By identifying and better understanding the many resources we all have available, we can ideally feel our best and more fully enjoy our lives both today and tomorrow. That is our hope and our commitment to every patient, so please let us know how we can help!
 
In health and healing,
Dr. Suzanne Gazda
 
 
Additional reflections…what about NAC in cases of long COVID and the vaccine injured?
 
We also recommend NAC in our long COVID and post-vaccine recovery protocols. Not only can NAC reduce oxidative stress and inflammation, but it has antiplatelet effects which can benefit the microclotting, endothelial activation, and platelet activation going on as a result of lingering spike protein. Studies also have shown that NAC may be a useful tool to degrade spike protein.  
 
In long COVID, spike protein not only causes direct damage to the mitochondria, but it also sets in motion a redox shift catalyzing high levels of oxidative stress and cellular compromise.  This unrelenting cycle drives inflammation, chronic fatigue, brain dysfunction, accelerated aging and much more. Reactive  oxidative species or ROS can trigger inflammation, damage the endothelium, lead to microthrombi and neuroinflammation, while promoting the formation of autoantibodies and disrupting neurotransmitter assembly. This unrelenting anabolism, the biochemical process in metabolism where the simple molecules combine to generate complex molecules, can lead to the formation of cytokine storms, chronic fatigue, chronic inflammation, or neurodegenerative diseases.   
 
For more about long COVID, please see our extensive series at: https://www.suzannegazdamd.com/blog---long-covid
 
References and additional reading:
 
Lauterburg BH, Corcoran GB, Mitchell JR. Mechanism of action of N-acetylcysteine in the protection against the hepatotoxicity of acetaminophen in rats in vivo. J Clin Invest. 1983;71(4):980-991. doi:10.1172/jci110853. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC436956/
 
Zhou Y, Danbolt NC. Glutamate as a neurotransmitter in the healthy brain. J Neural Transm (Vienna). 2014;121(8):799-817. doi:10.1007/s00702-014-1180-8
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4133642/
 
Olsen, N. How can antioxidants benefit our health? Medical News Today. (2018)
https://www.medicalnewstoday.com/articles/301506.php
 
Sampson, S. How does oxidative stress affect the body? Medical News Today. (2019)
https://www.medicalnewstoday.com/articles/324863
 
Barhoumi, T. et al. SARS-CoV-2 Coronavirus Spike Protein-Induced Apoptosis, Inflammatory, and Oxidative Stress Responses in THP-1-Like-Macrophages: Potential Role of Angiotensin-Converting Enzyme Inhibitor (Perindopril). (2021) https://www.frontiersin.org/articles/10.3389/fimmu.2021.728896/full?trk=public_post_comment-text
 
Sun, Q., Li, L., Jin, F. et al. SARS-CoV-2 Spike Protein S1 Exposure Increases Susceptibility to Angiotensin II-Induced Hypertension in Rats by Promoting Central Neuroinflammation and Oxidative Stress. Neurochem Res (2023). https://doi.org/10.1007/s11064-023-03949-1
 https://link.springer.com/article/10.1007/s11064-023-03949-1
 
Sampson, S. How much should I weigh for my height and age? Medical News Today. (2023)
https://www.medicalnewstoday.com/info/obesity/how-much-should-i-weigh.php
 
Cobley JN, Fiorello ML, Bailey DM. 13 reasons why the brain is susceptible to oxidative stress. Redox Biol. 2018;15:490-503. doi:10.1016/j.redox.2018.01.008
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5881419/
 
Cheignon C, Tomas M, Bonnefont-Rousselot D, Faller P, Hureau C, Collin F. Oxidative stress and the amyloid beta peptide in Alzheimer's disease. Redox Biol. 2018;14:450-464. doi:10.1016/j.redox.2017.10.014
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5881419/
 
Gazda, S. Alpha synuclein in neurodegenerative disease. suzannegazdamd.com (2020)
https://www.suzannegazdamd.com/scientifically-speaking1/alpha-synuclein-in-neurodegenerative-disease
 
Wu G, Fang YZ, Yang S, Lupton JR, Turner ND. Glutathione metabolism and its implications for health. J Nutr. 2004. https://www.sciencedirect.com/science/article/pii/S0022316623026639?via%3Dihub
 
Aoyama K. Glutathione in the Brain. Int J Mol Sci. 2021;22(9):5010. Published 2021 May 9. doi:10.3390/ijms22095010.
 
Le Gal K, Schmidt EE, Sayin VI. Cellular Redox Homeostasis. Antioxidants (Basel). 2021;10(9):1377. Published 2021 Aug 28. doi:10.3390/antiox10091377
 
Hara, Y. et al. Evaluation of the neuroprotective potential of N-acetylcysteine for prevention and treatment of cognitive aging and dementia. J Prev Alz Dis. (2017).
https://www.jpreventionalzheimer.com/all-issues.html?article=322
 
Farr SA, Poon HF, Dogrukol-Ak D et al. The antioxidants alpha-lipoic acid and N-acetylcysteine reverse memory impairment and brain oxidative stress in aged SAMP8 mice. J Neurochem. 2003. https://pubmed.ncbi.nlm.nih.gov/12603840/
Katz M, Won SJ, Park Y, et al. Cerebrospinal fluid concentrations of N-acetylcysteine after oral administration in Parkinson's disease. Parkinsonism Relat Disord. 2015;21(5):500-503. doi:10.1016/j.parkreldis.2015.02.020. https://pubmed.ncbi.nlm.nih.gov/25765302/
 
Wang HL, Zhang J, Li YP, Dong L, Chen YZ. Potential use of glutathione as a treatment for Parkinson's disease. Exp Ther Med. 2021;21(2):125. doi:10.3892/etm.2020.9557
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751460/
 
Bjørklund G, Peana M, Maes M, Dadar M, Severin B. The glutathione system in Parkinson's disease and its progression. Neurosci Biobehav Rev. 2021;120:470-478. doi:10.1016/j.neubiorev.2020.10.004. https://pubmed.ncbi.nlm.nih.gov/33068556/
 
Moon HE, Paek SH. Mitochondrial Dysfunction in Parkinson's Disease. Exp Neurobiol. 2015;24(2):103-116. doi:10.5607/en.2015.24.2.103. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4479806/
 
Martínez Banaclocha M. N-acetylcysteine elicited increase in complex I activity in synaptic mitochondria from aged mice: implications for treatment of Parkinson's disease. Brain Res. 2000;859(1):173-175. doi:10.1016/s0006-8993(00)02005-9.
 
Winston Tse-Hou Kwok, Haejin Angela Kwak, Ana Cristina Andreazza. N-acetylcysteine modulates rotenone-induced mitochondrial Complex I dysfunction in THP-1 cells. Mitochondrion. (2023). ISSN 1567-7249. https://doi.org/10.1016/j.mito.2023.07.001.
 
Monti, D. et al. N-Acetyl Cysteine May Support Dopamine Neurons in Parkinson's Disease: Preliminary Clinical and Cell Line Data. PLOS One. (2016).
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0157602
 
Monti, D.A., Zabrecky, G., Kremens, D., Liang, T.-W., Wintering, N.A., Bazzan, A.J., Zhong, L., Bowens, B.K., Chervoneva, I., Intenzo, C. and Newberg, A.B. (2019), N-Acetyl Cysteine Is Associated With Dopaminergic Improvement in Parkinson's Disease. Clin. Pharmacol. Ther., 106: 884-890. https://doi.org/10.1002/cpt.1548.https://ascpt.onlinelibrary.wiley.com/doi/10.1002/cpt.1548
 
Ohl K, Tenbrock K, Kipp M. Oxidative stress in multiple sclerosis: Central and peripheral mode of action. Exp Neurol. 2016;277:58-67. doi:10.1016/j.expneurol.2015.11.010
 
Shahrampour S, Heholt J, Wang A, et al. N-acetyl cysteine administration affects cerebral blood flow as measured by arterial spin labeling MRI in patients with multiple sclerosis. Heliyon. 2021;7(7):e07615. Published 2021 Jul 16. doi:10.1016/j.heliyon.2021.e07615
 
Schoeps, V.A., et al. N-Acetyl Cysteine as a Neuroprotective Agent in Progressive Multiple Sclerosis (NACPMS) trial: Study protocol for a randomized, double-blind, placebo-controlled add-on phase 2 trial. Contemporary Clinical Trials. Volume 122, 2022, 106941, ISSN 1551-7144.
https://doi.org/10.1016/j.cct.2022.106941.
https://www.sciencedirect.com/science/article/pii/S1551714422002671
 
Majdinasab, N. et al. The comparison of efficacy and safety of N-acetylcysteine and amantadine on fatigue, degree of disability, and quality of life of patients with MS that referred to the MS Association of Khuzestan Province. NeuroQuantology. (2022). Volume 20, Issue 16. Page 3432-3441| doi: 10.48047/NQ.2022.20.16.NQ880349.
 
Khalatbari Mohseni, G, Hosseini, SA, Majdinasab, N, Cheraghian, B. Effects of N-acetylcysteine on oxidative stress biomarkers, depression, and anxiety symptoms in patients with multiple sclerosis. Neuropsychopharmacol Rep. 2023; 00: 1– 9. https://doi.org/10.1002/npr2.12360
 
Marseglia L, Manti S, D'Angelo G, et al. Oxidative stress in obesity: a critical component in human diseases. Int J Mol Sci. 2014;16(1):378-400. Published 2014 Dec 26. doi:10.3390/ijms16010378
 
Rahmani F, Ghezzi L, Tosti V, et al. Twelve Weeks of Intermittent Caloric Restriction Diet Mitigates Neuroinflammation in Midlife Individuals with Multiple Sclerosis: A Pilot Study with Implications for Prevention of Alzheimer's Disease. J Alzheimers Dis. 2023;93(1):263-273. doi:10.3233/JAD-221007
 
Wang, Z. et al. Chronic Intermittent Fasting Improves Cognitive Functions and Brain Structures in Mice. PLOS One. (2013). https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0066069#s1
 
Farooq A, Herrera CP, Almudahka F, Mansour R. A Prospective Study of the Physiological and Neurobehavioral Effects of Ramadan Fasting in Preteen and Teenage Boys. J Acad Nutr Diet. 2015;115(6):889-897. doi:10.1016/j.jand.2015.02.012
 
Gibson, K.R., Winterburn, T.J., Barrett, F. et al. Therapeutic potential of N-acetylcysteine as an antiplatelet agent in patients with type-2 diabetes. Cardiovasc Diabetol 10, 43 (2011). https://doi.org/10.1186/1475-2840-10-43
 
Debnath U, Mitra A, Dewaker V, Prabhakar YS, Tadala R, Krishnan K, et al. N-acetyl cysteine: A tool to perturb SARS-CoV-2 spike protein conformation. ChemRxiv. Cambridge: Cambridge Open Engage. 2021. [preprint]
 
Amen Clinics. Memory and dementia. https://www.amenclinics.com/conditions/memory-problems-and-dementia/
 
Clough E, Inigo J, Chandra D, et al. Mitochondrial Dynamics in SARS-COV2 Spike Protein Treated Human Microglia: Implications for Neuro-COVID [published correction appears in J Neuroimmune Pharmacol. 2021 Dec 11;:]. J Neuroimmune Pharmacol. 2021;16(4):770-784. doi:10.1007/s11481-021-10015-6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487226/
 
Gazda, S. Antioxidant therapy with NAC for MS. suzannegazdamd.com. (2021)
https://www.suzannegazdamd.com/blog---ms-in-the-news/antioxidant-therapy-with-nac-for-ms
 
Gazda, S. What does gut health have to do with MS? suzannegazdamd.com. (2023) https://www.suzannegazdamd.com/blog---ms-in-the-news/what-does-gut-health-have-to-do-with-ms-research-shows-it-could-be-significant
 
Douglass, H. Increasing Glutathione Levels Lowers Alzheimer’s Pathology and Improves Cognitive Decline. UNSW – Centre for Healthy Brain Ageing. (2021).
https://cheba.unsw.edu.au/news/increasing-glutathione-levels-lowers-alzheimers-pathology-and-improves-cognitive-decline-0

If you’re not familiar with it, COSMOS or The COcoa Supplement and Multivitamin Outcomes Study is a clinical study that included over 21,000 subjects conducted at Brigham and Women’s Hospital, an affiliate of Harvard Medical School, Boston, and the Fred Hutchinson Cancer Research Center, Seattle. Scientists sought to understand more about the benefits of a daily 500 mg. cocoa extract supplement and a common multivitamin and whether the risk of heart disease, stroke, cancer, and other health conditions could be reduced with this protocol.
 
While the study team noted that more research is needed, the results specific to the cocoa extract, which is simply a flavonol (something we’ve often written about), were extremely promising: “long-term cocoa extract supplementation may favorably impact clinical cardiovascular outcomes, including a significant 27% reduction in cardiovascular death and greater cardiovascular benefits among those taking the study pills regularly.”
 
A bit of history and background.
 
Dating back to what is thought to be around 1000 BC, the history of chocolate is as captivating as the treat itself. Ancient Mesoamericans believed chocolate was an energy booster and aphrodisiac with mystical and medicinal qualities. The Mayans, who considered cacao a gift from the gods, used chocolate for sacred ceremonies and funeral offerings.
 
Cocoa is an ancient, fermented product made from the bean of the cacao tree, Theobroma cacao. Cocoa products contain catechins and epicatechins, which are readily water-soluble flavonoids (naturally occurring plant compounds) with vascular health benefits. Experimental and clinical studies testing the consumption of cocoa products and cocoa flavanols have noted potential benefits on platelet activation, endothelium-dependent vasodilation, blood pressure, inflammation, and insulin resistance, which may translate into important cardiovascular benefits.
 
Chocolate – good for the soul, and the heart and brain too!
 
First, it’s important to note that not all chocolate is created equal. So, before you grab a typical mass-produced, chocolate candy bar or bag of M&M’s (sorry, we know!), it’s important to understand that not all forms of chocolate contain the high levels of flavanols that have the benefits we want.
 
Dark, non-GMO (genetically modified organism) chocolate is best. Dark chocolate is lower in sugar and unhealthy saturated fat. To be classified as dark chocolate, it must contain at least 35% cocoa. However, I recommend choosing chocolate with the highest cocoa content, ideally 70% to 85%.  And, while it’s tempting to overdo it, remember that a little (up to 1 ounce daily) really does go a long way.
 
Not a big fan of sweets? Try a savory dish that stars dark chocolate:
https://www.allrecipes.com/article/chocolate-shows-savory-side-in-dinner-recipes/
 
Flavanols such as epicatechin mentioned above increase nitric oxide bioavailability that is crucial for regulating vascular function. This leads to improvements in vascular tone and improved regulation of blood pressure. These changes extend to brain perfusion or the net pressure gradient causing cerebral blood flow to the brain. This causes a better cerebrovascular coupling during neuronal activation, also essential for the structural and functional integrity of the brain. These processes also promote adult neurogenesis, the process by which new neurons are formed, in the hippocampus.
 
As noted in the COSMOS investigation, chocolate or cocoa does appear to have a number of cardiovascular benefits. Other research findings include:

• Women who ate chocolate had a significantly reduced risk of developing heart failure.
• A 2015 study of 21,000 people who were followed over 12 years found that the people who ate the most chocolate had an 11% lower incidence of coronary artery disease and a 25% lower incidence of cardiovascular death compared to people who did not eat chocolate.
• A 2016 study of more than 60,000 Swedish adults linked eating chocolate with a lower risk of heart attacks and ischemic heart disease.
• Eating dark chocolate with almonds improved blood lipid levels, such as cholesterol, in people with obesity. We know that there’s a link between high cholesterol and stroke risk so lowering cholesterol is a key part of any health program.

 
For the love of chocolate…You know that feel-good feeling you get when eating chocolate? That derives from the effect of four chemicals released by the brain including endorphins, serotonin, dopamine, and oxytocin. These chemicals, used by neurons to communicate with one another, create the positive emotions we experience. And chocolate also raises levels of phenylethylamine (PEA), “the love chemical,” which literally gets our heart pumping and increases feelings of joy.
 
Chocolate improves focus, memory, and learning.

The positive effects of chocolate have been extensively studied over the years. In 2017 for example, researchers foundthat consuming cocoa led to short- and long-term improvements in general cognition, attention, processing speed, and working memory as well.
 
More recently, the COSMOS study yielded the 2023 publication, “Dietary flavanols restore hippocampal-dependent memory in older adults with lower diet quality and lower habitual flavanol consumption.” Here, the authors conducted this extensive trial that included over 3,500 older adults who were randomly assigned to a three-year intervention of 500 mg. of cocoa flavanols per day, or a placebo (COSMOS). The results showed that flavanol consumption worked to support brain and memory performance during normal cognitive aging. Participants who started the trial with a lower flavanol intake diet and who took a cocoa extract supplement experienced an overall 24% increase in flavanol levels, on average, and achieved an average of 16% improvement in memory performance after one year, effectively catching up to those with a higher flavanol intake diet at the start of the study.
 
These results allow dietary flavanols to be considered in the context of a depletion–repletion paradigm and suggest that low flavanol consumption can act as a driver of the hippocampal-dependent component of cognitive aging. According to the study authors, “these results allow dietary flavanols to be considered in the context of a depletion–repletion paradigm and suggest that low flavanol consumption can act as a driver of the hippocampal-dependent component of cognitive aging.” The researchers emphasized the importance of this data and the hope that the information would lead to formal recommendations related to flavanol intake for brain health.
 
In addition to dark chocolate, there are several excellent sources of natural flavanols that we can easily incorporate as part of a healthy diet such as berries and citrus fruits, many vegetables, green tea, and others. 
 
Why we love flavonoids:
https://www.suzannegazdamd.com/blog/more-to-know-about-the-value-of-flavonoid

Antioxidants, compounds that protects cells from the damage caused by free radicals (unstable molecules made by the process of oxidation during normal metabolism), have been shown to reduce oxidative stress and neuroinflammation, therefore protecting those critical neurons. Some of those antioxidants have even been found to pass the blood-brain barrier (BBB) and enter the brain after eating cocoa.
 
Research has shown that cocoa and cocoa-derived products also may have neuromodulation and neuroprotective properties. Cocoa has been implicated to have the potential of counteracting cognitive decline and sustaining cognitive abilities through direct and indirect biological actions. Like other flavonoids it can interact with signaling proteins that are essential for pro-survival pathways that are crucial for triggering gene expression and protein synthesis in long-term potentiation. In the hippocampus area of the brain, which has a major role in learning and memory, flavonoids promote the expression of a protein called “brain-derived neurotrophic factor (BDNF).” BDNF is key in the process of adult neurogenesis, neuronal survival, and synaptic growth – so protecting it is crucial to the wellbeing of our neurological functions.

Efforts to resolve her condition failed and it wasn’t until more than 20 years later it was determined she actually had lupus as well as schizophrenia. At this point and months of appropriate treatments later, her condition finally began to improve.
 
The article, “A catatonic woman awakened after 20 years. Her story may change psychiatry,” details the patient’s and her family’s struggles and discusses research that has shown how a subset of patients with some psychiatric conditions such as schizophrenia may actually have autoimmune disease that attacks the brain. Scientific teams in other countries are also pursuing investigations and finding that underlying autoimmune and inflammatory processes may be more common in patients with a variety of psychiatric syndromes than previously believed.
 
I have written at length about the link between autoimmune disorders and neuropsychiatric conditions including these and several other related articles:
 
What causes our body to attack the mind?
 
A rising tide of anxiety and depression disorders demand we look first at the causal mechanisms.
 
The dysregulated immune system response – when neural signaling goes awry.
 
Be the change for better education about neuropsychiatric disease.
 
Immune dysregulation requires rapid response to affect better outcomes.
 
Is there more to immune-mediated dysfunction in even more neurological disorders?
 
I encourage you to read the article about this young woman’s health journey to gain a better understanding of just how critical it is to understand the impact of autoimmune disease on our brain and other vital systems. Please visit our website and blog library for additional reading – and as always, let us know if you have questions or concerns!
 
In hope and healing for all,
Dr. Suzanne Gazda
 
Reference:
 
Sima, R. A catatonic woman awakened after 20 years. Her story may change psychiatry. The Washington Post. (June 1, 2023). https://www.washingtonpost.com/wellness/2023/06/01/schizophrenia-autoimmune-lupus-psychiatry/

Now comes even more evidence as to why this artificial sweetener is so damaging to our neurological wellbeing and is something that should have been made widely known a long time ago.
 
Newly released findings from the World Health Organization (WHO) recommend against the use of non-sugar substitutes (NSS) to control body weight or reduce the risk of noncommunicable diseases (NCDs). Their systematic review concluded that “use of NSS does not confer any long-term benefit in reducing body fat in adults or children. Results of the review also suggest that there may be potential undesirable effects from long-term use of NSS, such as an increased risk of type 2 diabetes, cardiovascular diseases, and mortality in adults.”
 
The WHO guidelines on NSS are part of a suite of current and future guidelines regarding healthy diets and the need to establish lifelong healthy eating habits that improve dietary quality, and ideally decrease the risk of NCDs worldwide.
 
However, we must raise the question that in the face of enormous evidence that has existed for decades about the danger of aspartame and other food additives, why are these guidelines only now being issued? Dr. Russell Blaylock is a neurosurgeon who for years has spoken out about the serious health concerns surrounding aspartame. In his book,Excitotoxins: The Taste That Kills, Blaylock looks in detail at over 500 studies that clearly identify aspartame as being one of the most dangerous yet widely available substances and has been linked to over 75% of the adverse reactions to food additives as reported to the Food and Drug Administration (FDA) such as:

• Migraines
• Brain fog
• Dizziness 
• Memory loss
• Insomnia
• Fatigue
• Weight gain
• And others, as well as more serious reactions including seizures and even fatalities.

 
In an article published on “U.S. Right to Know,” author Stacy Malkin writes about aspartame and the decades of science that point to serious health risks. Malkin notes that aspartame is found in over 6,000 products, from diet sodas and reduced-calorie beverages to chewing gum and candies. But, since aspartame was first introduced in 1974, numerous studies have pointed to its link in diseases such as Alzheimer’s, cancer, stroke, dementia, intestinal dysbiosis, neurotoxicity and mood disorders, as well as cardiovascular and additional serious conditions.
 
Harvard University had several years ago advised pregnant women to avoid artificial sweeteners including aspartame, citing a study of 3,000 subjects that indicated the potential for excessive weight gain in the mothers and subsequently in the babies as well. As we know, obesity can bring with it a host of health issues that can affect many of our systems and contribute to developing other disorders. Even when dietary factors were controlled, there was still a correlation between higher consumption of diet beverages and increased fetal weight.
 
So, why are we still surrounded by product choices replete with aspartame and harmful additives like monosodium glutamate (MSG), and other non-nutritional chemicals? And why did it take the WHO so long to put forward their recent guidelines? Unfortunately, the answers point to the nature of our economies in this and other countries, the influence of huge corporations, and the immense power of large pharmaceutical companies…which can often mean that what’s best for our health is far down the list of important concerns. 
 
It’s up to each of us to use the information at hand to make the right decisions for ourselves and our loved ones, choosing fresh over processed foods, limiting sugar and other products that can provoke inflammation, trying to get about 7 hours of quality sleep each night, exercising and getting out in nature. And those are the sweetest things you can do for the sake of your beautiful brain!
 
In hope and healing,
Dr. Suzanne Gazda
 
For additional related reading, please visit our blog library for these titles and more:
 
https://www.suzannegazdamd.com/blog/what-how-we-eat-now-could-determine-our-future-brain-health
 
https://www.suzannegazdamd.com/blog/autoimmune-diseases-and-aging-its-not-just-about-your-family-tree
 
https://www.suzannegazdamd.com/blog/eating-well-for-life
 
References:
 
Gazda, S. Aspartame: a toxin to avoid for your brain’s wellbeing. SuzanneGazdaMD.com. (2022) https://www.suzannegazdamd.com/blog/aspartame-a-toxin-to-avoid-for-your-brains-wellbeing
 
World Health Organization. WHO advises not to use non-sugar sweeteners for weight control in newly released guideline. WHO International News Release. (May 15, 2023)
https://www.who.int/news/item/15-05-2023-who-advises-not-to-use-non-sugar-sweeteners-for-weight-control-in-newly-released-guideline
 
Blaylock, R. Excitotoxins: The Taste That Kills. (2011)
https://www.amazon.com/Excitotoxins-Taste-Russell-L-Blaylock/dp/144179445X
 
Malkan, S. Aspartame: Decades of science point to serious health risks. U.S. Right to Know. (May 15, 2023). https://usrtk.org/sweeteners/aspartame_health_risks/
 
McCarthy, C. Why pregnant women should avoid artificially sweetened beverages. Harvard Health Publishing, Harvard Medical School. (2016).
https://www.health.harvard.edu/blog/pregnant-women-avoid-artificially-sweetened-beverages-201605179714

Researchers set out to evaluate brain volume changes caused by different sub-classes of anti-amyloid beta (Aβ) drugs trialed in patients with Alzheimer's disease. This systematic review and meta-analysis included adults enrolled in randomized controlled trials of anti-Aβ drugs. Anti-amyloid treatments work by attaching to and removing beta-amyloid, a protein that accumulates into plaques, from the brain. Each works differently and targets beta-amyloid at a different stage of plaque formation.
 
The review team noted “these findings reveal the potential for anti-Aβ therapies to compromise long-term brain health by accelerating brain atrophy” and brain volume loss, as well as risk of intracranial bleeding. Additionally, they concluded that their review could provide new insight into the adverse effects of Amyloid-Related Imaging Abnormalities (ARIA).
 
It’s critical to understand too that while certain medications currently available, such as memantine and donepezil, may reflect some efficacy in reducing symptoms, they do not actually slow disease progression.   
 
What else we should know - and what we can do.
 
The expectation that medication alone can alter the course of any disorder is simply not realistic. Modifying our lifestyle habits, such as increasing regular activity levels and adopting healthy dietary plans, are equally important factors whether or not we have a neurological, cardiac, autoimmune, or other condition.
 
I have discussed at length and recommend The Bredesen Protocol, which has been shown to potentially reverse signs of dementia. In a 2022 published study, Drs. Dale Bredesen and Kat Toups led a team of esteemed researchers “to determine whether a precision medicine approach to Alzheimer's disease and mild cognitive impairment is effective enough in a proof-of-concept trial to warrant a larger, randomized, controlled clinical trial.”
 
Their results: All outcome measures revealed improvement: statistically significant improvement in MoCA scores, CNS Vital Signs Neurocognitive Index, and Alzheimer's Questionnaire Change score were documented. No serious adverse events were recorded. MRI volumetrics also improved. Based on the cognitive improvements observed in this study, the investigating team concluded that a larger, randomized, controlled trial of the precision medicine therapeutic approach described was definitely warranted.
 
Other clinicians, including those whose treatment practices follow a different approach, support the idea that positive dietary and lifestyle interventions should be part of a comprehensive approach, much like we have pursued in treating other disorders such as heart disease and diabetes.
  
You can download the Bredesen Protocol reference guide on our website, where you’ll also find a wealth of related reading about other neurological and autoimmune diseases, wellness, and much more.
 
As always, we encourage you to review concerns or questions with your physician regarding making any changes to current therapies. And please feel free to reach out to our offices if you would like to schedule a visit – we are here to help!
 
In hope and healing,
Dr. Suzanne Gazda
 
References:
 
Alzheimer's Association – Understanding Treatments and Research
https://www.alz.org/help-support/i-have-alz/treatments-research
 
Alves, F. et al. Accelerated Brain Volume Loss Caused by Anti–β-Amyloid Drugs: A Systematic Review and Meta-analysis. Neurology. 2023. DOI: 10.1212/WNL.0000000000207156.
 
Blanco-Silvente, L., Capellà, D., Garre-Olmo, J. et al. Predictors of discontinuation, efficacy, and safety of memantine treatment for Alzheimer's disease: meta-analysis and meta-regression of 18 randomized clinical trials involving 5004 patients. BMC Geriatr 18, 168 (2018). https://doi.org/10.1186/s12877-018-0857-5
 
Knowles J. Donepezil in Alzheimer's disease: an evidence-based review of its impact on clinical and economic outcomes. Core Evid. 2006;1(3):195-219.
 
Toups K, Hathaway A, Gordon D, et al. Precision Medicine Approach to Alzheimer's Disease: Successful Pilot Project. J Alzheimers Dis. 2022;88(4):1411-1421. doi:10.3233/JAD-21570
 
The Bredesen Protocol and Alzheimer's.
https://www.today.com/health/how-prevent-alzheimer-s-reduce-risk-foods-lifestyle-t189658
 
Additional reading:
 
Eat well today for a brighter cognitive future.
https://www.suzannegazdamd.com/blog/what-how-we-eat-now-could-determine-our-future-brain-health
 
Keto diet.
https://www.suzannegazdamd.com/blog/a-ketogenic-diet-can-it-be-beneficial-for-our-brains-and-our-bodies
 
Olive oil and brain health.
https://www.suzannegazdamd.com/blog/olive-oil-the-heart-of-the-mediterranean-diet-thats-good-for-your-brain-too
 
Vitamin D and neurodegenerative disease.
https://www.suzannegazdamd.com/blog/vitamin-d-deficiency-linked-to-neurodegenerative-disease

Scientists noted that their study results further emphasize the need to maintain functional vitamin D levels in the management of acute ischemic stroke, which occurs when a blood vessel supplying the brain becomes blocked, as by a clot. In our practice, we generally recommend maintaining levels between 60 and 100 ng/mL in most of patients.
 
Several large observational reviews clearly show how vitamin D deficiency, an unrecognized global epidemic, is associated with increased risks and unfavorable outcomes of a variety of conditions, like cardiovascular andautoimmune disease, some cancers, and neurological disorders.
 
Cumulative evidence indicates that vitamin D can ameliorate neurodegeneration by regulating pertinent molecules and signaling pathways including maintaining Ca2+ homeostasis, reducing oxidative stress, inhibiting inflammation, suppressing the formation and aggregation of the pathogenic protein, and more. 
                                                               
The potentially shrinking brain.
 
It’s not just evidence from modern-day studies that underscores the importance of vitamin D for brain and general health. Several researchers have contended that over time the size of the average human brain has indeed decreased. John Hawks of the University of Wisconsin long held this view, as did Christopher Stringer, a paleoanthropologist at the Natural History Museum, London. And, more recently, Jeremy DeSilva, paleoanthropologist at Dartmouth College, produced a paper after studying 987 skulls that dramatically concluded that the brain size of human ancestors increased 2.1-1.5 million years ago, but started to sharply decrease 3,000 years ago, and is now a lemon smaller. However, it’s important to note that this claim has been refuted by other scientists, notably Brian Villmoare, anthropologist at the University of Nevada, Las Vegas, who contend that the brains examined in DeSilva’s study only represent a small sample in number and years.
 
But, if the human brain is shrinking in size to any degree, then should we consider the role of negative environmental factors? Just some of these impacts include higher Co2 levels, chemicals, toxins, air pollution, the Western diet, GMOs, pesticides, EMFs, stress, lack of adequate sleep, high levels of aluminum from a variety of sources, AND low levels of vitamin D. 
 
There are a number of key points that revolve around the question of brain size changes over the course of history:
 
•Our human brain evolved in a linear fashion up to about 250,000 years ago, when (for reasons that remain a mystery) a sudden, explosive period of growth gave us a neocortex much larger and denser than that of any other species. 
•Technology is evolving, but our brain is not. 
•The human brain evolved when Co2 levels were lower.
•It has been ascertained that the human brain decreased from 1,500 cubic centimeters (cc) to 1,350cc, irrespective of gender and race.
If we continue along this path that impacts the ability to maintain adequate levels of vitamin D, we could end up having the same-sized brain as Homo erectus, an ancient human species which had a brain estimated to measure only 1,100 cc.
 
Brain aging in youth and adults alike.
 
Vitamin D is just one modifiable factor that influences brain health and potentially brain aging. Additional research also underlies the role of vitamin D deficits in accelerated brain aging. In a German population-based cohort study with over 1,800 participants aged 20 to 82, there was a direct correlation between adverse aging in subjects whose vitamin D levels were lacking. While this was primarily significant in older populations, the association in younger subjects was still relevant. Researchers noted that “in summary, our results support previous findings suggesting that vitamin D-deficient individuals have advanced brain aging.”
 
There are additional concerns particularly in our youth populations that arose in recent years and included:
•As a result of social isolation and distancing during the shut-down, virtually all youth experienced adversity in the form of significant departures from their normal routines. In addition, financial strain, threats to physical health, and exposure to increased familial violence were alarmingly common during the pandemic.
•A small study comparing brain scans of young people from before and after 2020 reveals that the brains of teens who lived through the pandemic look about three years older than expected
•Compared to carefully matched peers assessed before the pandemic, adolescents assessed during the pandemic showed signs of advanced cortical thinning and had larger bilateral hippocampal and amygdala volumes.
 
Vitamin D deficiency is a universal problem.
 
One issue that particularly affects our ability to naturally maintain healthy levels of vitamin D is an emphasis on indoor lifestyles, about which we have previously written at length. A reliance on technology devices and entertainment that takes place in front of televisions instead of in backyards or at playgrounds has truly put our children at risk of deficiencies that are not always identified. Less exposure to sunlight through outdoor play and/or poor-quality diets, even in countries with ample food sources, make it more important to consider supplements. But that’s often a problem in parts of the world where access is limited or nonexistent.
 
Vitamin D is a fat-soluble vitamin that depends on the gut's ability to absorb dietary fat. People who are obese tend to have lower blood vitamin D levels. And while Vitamin D accumulates in excess fat tissues, it is not easily available for use by the body when needed. Additional environmental factors, even the latitude at which we live along with air pollution, can also affect vitamin D synthesis. 
 
Patients with conditions including neurological and neuroautoimmune disorders are advised to obtain measurements of their vitamin D levels and based on individual health needs, consider the value of adding a high-quality vitamin D3 supplement. But always talk to your physician before adding or changing your current regimen. 
 
Most importantly, you and your family should try to spend some time outdoors every day. There are so many benefitseven beyond the power of sunlight that come from getting out in nature. Your brain and your body will thank you!
 
In hope and healing,
Dr. Suzanne Gazda
 
Additional reading:
 
Gazda, S. More studies point to critical importance of vitamin D in immune health. 2020.
https://www.suzannegazdamd.com/blog/more-studies-point-to-critical-importance-of-vitamin-d-in-immune-health
 
Gazda, S. The indoor generation is missing out on vitamin D. 2021.
https://www.suzannegazdamd.com/blog/the-indoor-generation-is-missing-out-on-vitamin-d
 
References:
 
Cui, P. et al. Microglia/macrophages require vitamin D signaling to restrain neuroinflammation and brain injury in a murine ischemic stroke model. J of Neuroinflammation. March 2023.
https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-023-02705-0
 
Menon V, Kar SK, Suthar N, Nebhinani N. Vitamin D and Depression: A Critical Appraisal of the Evidence and Future Directions. Indian J Psychol Med. 2020;42(1):11-21. Published 2020 Jan 6. doi:10.4103/IJPSYM.IJPSYM_160_19.
 
Schmerling, R. Can vitamin D supplements prevent autoimmune disease? Harvard Health Publishing. 2022.
https://www.health.harvard.edu/blog/can-vitamin-d-supplements-prevent-autoimmune-disease-202203242712  
 
Wang W, Li Y, Meng X. Vitamin D and neurodegenerative diseases. Heliyon. 2023;9(1):e12877. Published 2023 Jan 12. doi:10.1016/j.heliyon.2023.e12877
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9938420/
 
 
Cannon JR, Greenamyre JT. The role of environmental exposures in neurodegeneration and neurodegenerative diseases. Toxicol Sci. 2011;124(2):225-250. doi:10.1093/toxsci/kfr239
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3216414/
 
Beyond Pesticides, Daily News Blog. Retrieved March 2023.
https://beyondpesticides.org/dailynewsblog/2022/08/new-evidence-shows-roundup-damages-the-nervous-system/
 
Duhani, I. The effects of electromagnetic fields on human health. Physica Medica. 2016.
 
Liu, C. et al. Increasing breadth of the frontal lobe but decreasing height of the human brain between two Chinese samples from a Neolithic site and from living humans.” American Journal of Physical Anthropology. 2014.
 
Kisielinkski, K. et al. Possible toxicity of chronic carbon dioxide exposure associated with face mask use, particularly in pregnant women, children and adolescents – A scoping review. Heliyon. March 2023. 
 
Allen, J. et al. Associations of Cognitive Function Scores with Carbon Dioxide, Ventilation, and Volatile Organic Compound Exposures in Office Workers: A Controlled Exposure Study of Green and Conventional Office Environments. Env Health Perspective. 2016 

For example, while a single 12-ounce soda may indicate it contains just 150 calories, 140 of those come from a whopping 39 grams or almost ten teaspoons of sugar! But, as you’ll see below, sugar substitutes like aspartame are not a “healthier” choice either. And as research has shown, aspartame can indeed be detrimental to brain health.
 
No one would argue about the negative impacts of sugar-laden sodas and other products, such as highly processed convenience foods and snacks. Over-consumption of sugar can contribute to increased systemic inflammation that we know is at the root of virtually every disease, including neurological and cardiovascular conditions. Current data indicates that the average American youth consumes roughly 81 grams of sugar per day and American adults consume an average of 77 grams of sugar per day, amounting to nearly eight teaspoons each day.
 
The general guidelines recommend that:

• Men should consume no more than nine teaspoons (36 grams or 150 calories) of added sugar per day.
• For women, the number is lower: six teaspoons (25 grams or 100 calories) per day. 

 
But, for perspective, measure out six to nine teaspoons in a bowl. Visually, that just seems like an awful lot of sugar we’re putting in our bodies on a regular basis! So why are all the marketing campaigns over the years, like that popular advertising tune, “I'd like to buy the world a Coke,” making it seem as if all of life’s events should be accompanied by a soda and encouraging people to have a big gulp of entirely too much sugar? Combined with what can be limited access to fresh, whole foods, it’s no wonder that as a nation so many people are suffering the challenges of obesity.
 
It is estimated now that nearly one in three adults (30.7%) are overweight and two out of five are obese; in children, approximately one of six are overweight and one out of five are obese.     
 
Diet sodas:  A not-so-healthy alternative.
 
But, what about those Diet Cokes and other reduced-calorie sodas that so many choose as a 
“healthier choice?” The Coca-Cola Company first introduced Diet Coke in 1982 and in 1983 began using aspartame as the drink’s artificial sweetener ingredient.

What are the risks?
 
Dozens of studies have linked aspartame — the world’s most widely used artificial sweetener — to serious health problems, including cancer, cardiovascular disease, Alzheimer’s disease, seizures, stroke and dementia, as well as negative effects such as intestinal dysbiosis, mood disorders, headaches, and migraines.
 
People drinking diet soda daily were almost three times as likely to develop stroke and dementia as those who consumed it weekly or less. This included a higher risk of ischemic stroke, where blood vessels in the brain become obstructed, and Alzheimer’s disease dementia, the most common form of dementia, as reported in a 2017 study in Stroke.
 
In a 2012 study in the Journal of General Internal Medicine, participants who drank diet soft drinks daily had an increased risk of vascular events compared to those who drank no diet beverages.
 
Researchers at the University of Iowa found similar results by analyzing data from the Women's Health Initiative (WHI), which tracked the medical histories and health habits of more than 93,000 women. In comparing women who consumed two or more diet drinks a day to those who never or occasionally did, they showed that diet beverage drinkers were 30% more likely to have a cardiovascular event and 50% more likely to die from a related disease.
 
And, a recent study published September 2022  in the BMJ, which involved more than 100,000 adults in France, found a potential link between consumption of artificial sweeteners and heart disease.
 
Aspartame also has been linked to behavioral and cognitive problems including learning problems, headache, seizure, migraines, irritable moods, anxiety, depression, and insomnia, wrote the researchers of a 2017 study in Nutritional Neuroscience.
 
Aspartame identified as a neurotoxin that changes the brain now and for future generations.
 
A new study finds that the consumption of aspartame, a widely used artificial sweetener, produces anxiety-like behavior in mice, along with epigenetic changes in the amygdala.  The amygdala is a part of the brain associated with regulating anxiety and fear. These changes persisted for up to two subsequent generations. The study’s findings point to follow-up research regarding aspartame and anxiety in humans.
 
After learning more about aspartame, I recommend that patients avoid this product that is clearly toxic to the body and the brain. Things go better without a Coke, or any other diet soda that uses chemical replacements for sugar. Talk to your doctor about alternatives, like sparkling waters flavored with fruit essence or a slice of citrus, unsweetened green, black, or herbal tea, and other healthful options! 

​In health and healing,
Dr. Suzanne Gazda

References:  
 
Harvard Health Publishing – The sweet danger of sugar.
https://www.health.harvard.edu/heart-health/the-sweet-danger-of-sugar
 
National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases
https://www.niddk.nih.gov/health-information/health-statistics/overweight-obesity
 
Eat this, not that: diet sodas
https://www.eatthis.com/drinking-diet-soda-bad-for-you-doctors/
 
Centers for Disease Control and Prevention
https://www.cdc.gov/nchs/products/databriefs/db109.htm
 
Aspartame Facts
https://aspartame.org/aspartame-products/#.VNO3MFXF_w4
 
The Health Risks of Aspartame
https://usrtk.org/sweeteners/aspartame_health_risks/#history
 
Pase, M. et al. Sugar- and Artificially Sweetened Beverages and the Risks of Incident Stroke and Dementia: A Prospective Cohort Study. Stroke. 20 April 2017. https://www.ahajournals.org/doi/10.1161/STROKEAHA.116.016027
 
Vyas, A., Rubenstein, L., Robinson, J. et al. Diet Drink Consumption and the Risk of Cardiovascular Events: A Report from the Women’s Health Initiative. J GEN INTERN MED 30, 462–468 (2015). https://doi.org/10.1007/s11606-014-3098-0
 
Debras C, Chazelas E, Sellem L, Porcher R, Druesne-Pecollo N, Esseddik Y et al. Artificial sweeteners and risk of cardiovascular diseases: results from the prospective NutriNet-Santé cohort BMJ 2022; 378 :e071204 doi:10.1136/bmj-2022-071204
https://www.bmj.com/content/378/bmj-2022-071204
 
 
Czarnecka K, Pilarz A, Rogut A, et al. Aspartame-True or False? Narrative Review of Safety Analysis of General Use in Products. Nutrients. 2021;13(6):1957. Published 2021 Jun 7. doi:10.3390/nu13061957
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227014/

As we wrote in our previous blog, flavonoids been well documented for their various health- promoting effects. ​

In regard to brain health, these naturally occurring phytonutrients exert multiple neuroprotective actions, such as protection of neurons from neurotoxins, suppression of neuron-inflammation and thus improve memory, learning and cognitive function
 
The flavonoids-rich foods such as green tea, cocoa, blueberries, and other foods improve the various states of cognitive dysfunction. More than 7,000 flavonoids have been reported from natural sources including medicinal plants, vegetables, fruits and wines. 
 
Flavonoids can increase brain cell function and neuronal survival by reducing oxidative stress, activating neurotrophic factor signaling pathways, preventing alterations in protein processing, reducing synaptic dysfunction, and inhibiting inflammatory responses.  Flavonoids are also anti-apoptotic and may have anticancer activity by their ability to inhibit cell proliferation and induce apoptosis and autophagy. Researchers have found that flavonoids can dampen the progression of pathological symptoms of neurodegenerative diseases by inhibiting neuronal apoptosis (death) induced by neurotoxic substances including free radicals and β-amyloid proteins (Aβ).
 
Additionally, they enhance vascular blood flow and enhance nerve cell growth particularly in the hippocampus, called the primary memory center of the brain.

Alzheimer’s disease: shall we have a cup of tea?  
 
Extensive investigations have noted that flavonoids attenuate the initiation and progression of AD-like pathological symptoms and related neurodegenerative disorders.
 
Flavonoids including epicatechin-3-gallate (EGCG is found in green tea), gossypetin ( red hibiscus flower) , quercetin and myricetin (a flavonoid found in tea, berries, fruits, wine, and herbs) are reported to block β-amyloid, and tau aggregation, scavenge free radicals and sequester metal ions at clinically low concentrations.

Looking for more ways to savor delicious and healthful tea? Check here for an easy recipe!
https://amosinstitute.com/blog/cheers-to-brain-health-a-drink-to-improve-memory/
​

• Quercetin 

Quercetin produces a reduction in plaque burden and mitochondrial dysfunction through the activation of AMPK (a cellular energy sensor) and may be one of the mechanisms by which quercetin improves cognitive functioning (note that with AMPK activation, the downstream affects include improved mitochondrial metabolism and reduction in inflammation). Quercetin also has anti-inflammatory and neuroprotective effects and helps with endothelial damage and can cross and strengthen the BBB. 
Onions contain the highest levels — lower levels can be found in broccoli, blueberries, cauliflower, curly kale, leeks, spinach and strawberries.

• Kaempferol

This flavonoid, kaempferol, appears to inhibit the growth of cancer cells while preserving and protecting normal cells. Kaempferol attenuates cognitive deficit via regulating oxidative stress and neuroinflammation. Good sources of kaempferol are onions, asparagus and berries, but the richest plant sources are spinach, kale and other green leafy vegetables, as well as herbs such as chives, dill and tarragon.

• Myricetin

Myricetin has been studied in rodents for blood sugar control and the reduction of tau, a protein that causes the hallmark tangles of Alzheimer’s and other dementia. It has been shown to be effective in inhibiting acetylcholinesterase, which breaks down acetylcholine in the brain and it upregulates brain-derived neurotrophic factor and nerve growth factor. BDNF and NGF are crucial neurotrophic factors involved in the protection of nerve cells against stress. Spinach and strawberries contain high levels of myricetin, but honey, black currants, grapes and other fruits, berries, vegetables, nuts and tea are also good sources.

• Isorhamnetin 

This flavonol, isorhamnetin, may protect against cardiovascular and neurovascular disease in addition to anti-tumor and anti-inflammatory benefits. The protective effect of isorhamnetin includes anti-inflammation, anti-oxidative stress and anti-apoptosis. Good sources of isorhamnetin are pears, olive oil, wine, and tomato sauce.

• Gossypetin: 

A recent study showed that gossypetin (also known as Hibiscus sabdariffa or roselle) found in hibiscus activates microglia, the resident immune cell in the brain.
Accumulation of toxic aggregates of the beta-amyloid proteins in certain brain regions is often linked to the decline in cognitive function characteristic of Alzheimer’s disease.
 
Microglia (the brains primary immune cells) constantly scavenge various waste materials in the brain including damaged or apoptotic neurons and Aβ. Through phagocytosis of Aβ, microglia prevent the accumulation of Aβ plaque in the brain. When the microglia scavenge amyloid-beta (Aβ) in the brain, this helps ameliorate cognitive impairments brought on by Alzheimer's disease.
 
A recent study conducted in mice suggests that gossypetin, a compound derived from the flower of the roselle plant, which is a hibiscus species, also may hold promise as a therapeutic agent for Alzheimer’s.

• Citrus flavonoids

These flavonoids, such as naringenin and hesperidin, both can cross the BBB and prevent neuronal deterioration; naringenin also inhibits the production of nitric oxide in the activated microglia cells. It is mainly present in grapefruits and sour oranges, while hesperidin is present in sweet oranges, mandarins and lemons.
 
This study showed hesperidin also has affinity for the molecular docking site in SARS CoV 2 and, as such, it may hold promising antiviral properties.

• Curcumin

Curcumin has long been known as the Spice of Life because of it’s very important proprieties such as anti-oxidant, anti-inflammatory, anti-microbial, antiproliferative, anti-tumoral, and anti-aging.  The protective effectof curcumin against some neurodegenerative diseases has been proven by in vivo and in vitro studies.  Curcumin can target the two pathological hallmarks of Alzheimer’s disease ie amyloid and tau. Curcumin has shown promise in animal models in the treatment of Parkinson’s disease and MS. 
 
Only a limited number of clinical studies have examined curcumin’s effect on human cognitive functioning, and the results are inconclusive. Researchers are nearly unanimous in their opinion that a combination of curcumin with other dietary supplements, such as piperine, α-lipoic acid, N-acetylcysteine, B vitamins, vitamin C, and folate, has a synergistic effect and enhances its neuroprotective effects. 
 
The BBB is the major obstacle for the delivery of curcumin into the brain, limiting its therapeutic potential. The native form of curcumin is BBB permeable, but once it has undergone biotransformation (metabolized into glucuronides), the ability to pass the barrier is lost since the conjugated metabolites are bulky water-soluble molecules and undergoes quick renal clearance.
 
The formulation of curcumin-galactomannan complex is thought to have improved central nervous system (CNS) distribution.  CurQfen®, a new generation curcumin for brain health, a green formulation of curcumin and de-bitterised fenugreek fiber as self-emulsifying hydrogel scaffold, is capable of delivering high level of BBB-permeable ‘free curcumin’ even at a low dosage of 250mg single dose.
 
BCM-95® is a patented curcumin formula that combines curcumin and volatile agents in turmeric essential oil to increase bioavailability. The formula is also comprised of lecithin and medium chain triglycerides to further assist in this process. Turmeric essential oil constitutes approximately 9% of the formulation. 
 
A 2021 study, published in Antioxidants, built on ample previous studies demonstrating the powerful antioxidant, anti-inflammatory, and anti-amyloid properties of curcumin with a product called CURCUGREEN's (BCM-95).

• Grape Seed Extracts 

Grape seed contains several flavonoids and non-flavonoids and exerts potent antioxidant and anti-inflammatory effects.   GSE has been shown to improved blood pressure, blood flow, reduces oxidative stress inhibit the formation of amyloid and other neurotoxins. It is water-soluble and can cross the blood-brain barrier more easily than other natural antioxidants.
 
A 12-week study in 111 healthy older adults found that taking 150 mg of GSE daily improved attention, language, and both immediate and delayed memory 

• Propolis 

Propolis is a natural bee product and a very good source of polyphenols
It has been shown that the active components of propolis have high binding potential to cellular Angiotensin-converting enzyme-2 (ACE-2) receptors of the S1 spike protein and also has immunomodulatory, anti-thrombosis activities.
 
Flavonoids as cholinesterase inhibitors.
 
In the brain of a person with Alzheimer’s disease, there are lower levels of a chemical called acetylcholine. Acetylcholine helps to send messages between certain nerve cells. In Alzheimer’s disease some of the nerve cells that use acetylcholine are also lost. 
 
The pharmaceutical products like donepezil, rivastigmine and galantamine all prevent an enzyme called acetylcholinesterase from breaking down acetylcholine. This means there is a higher concentration of acetylcholine in the brain, which leads to better communication between nerve cells.
 
Flavonoids also can inhibit this enzyme (acetylcholinesterase (AChE) and help restore acetylcholine (ACh) which is vital for memory by drawing upon their established antioxidant activity, which subsequently could be helpful for Alzheimer’s treatment.

• Quercetin was found most active and exhibiting a 76.2% inhibition of AChE.
• Myricetin has been shown to be effective in inhibiting acetylcholinesterase, which breaks down acetylcholine in the brain.
• Ashwagandha extract also has been found to inhibit acetylcholinesterase.
• Luteolin was effective, but also has been shown to decrease the formation of Aβ peptides.

 
Flavonoids in long COVID. 
 
Given all of these beneficial properties and study-proven effects, it is believed that flavonoids could be helpful in treating long COVID and post-vaccine injuries. Of note, a recent study found that oral PEA-LUT 700 + 70 mg administered bid for eight weeks increased the GABABergic activity and cortical plasticity. PEA belongs to the family of endocannabinoids, naturally produced in the body, and largely found in several food sources which can exert anti-inflammatory and neuroprotective effects.
 
Another study found that palmitoylethanolamide and luteolin (PEA-LUT) have anti-inflammatory and neuroprotective properties; the dose used was PEA-LUT (700 mg + 70 mg) per day. PEA also confers neuroprotection in the CNS by shifting microglia from the M1 pro-inflammatory phenotype to M2 anti-inflammatory phenotype. Luteolin, a flavonoid with anti-inflammatory and neuroprotective properties, exerts its effects through neurotrophic and antioxidant mechanisms. Luteolin increases the expression of the brain-derived neurotrophic factor (BDNF), which supports neuronal survival, growth, and plasticity. Additional research also looked at the value of plant-based compounds, specifically pomegranate peel extract, as a possible novel antiviral therapy.
 
Can flavonoids help with spike protein burden?
 
Flavonoids such as quercetin, myricetin, baicalin, propolis, hesperidin and epigallocatechin gallate (EGCG), have the ability to prevent spike protein from binding to the ACE 2 receptor. 
Dandelion tea also effectively binds to this docking site preventing spike protein from binding to the ACE 2 receptor. 
 
With their beneficial anti-inflammatory effects and ability to protect cells oxidative damage, flavonoids can be an integral part of your efforts to help ensure optimal brain and overall health. They can help the body function more efficiently while protecting it against everyday toxins and stressors. 
 
As always, we encourage you to consult your physician before making any dramatic changes or additions to your current diet – especially if you are taking prescribed medications for other conditions. While it’s preferred we get our nutrients from whole, fresh food, if you do choose to supplement make sure you opt for a high quality brand for more assurance it contains the stated ingredients. 
 
Let us know if you have questions or if we can provide any additional information – we’re here to help!
 
In health and healing,
Dr. Suzanne Gazda
 
 
For more related reading from our blog archives:
 
https://www.suzannegazdamd.com/blog/study-finds-therapeutic-antiviral-effects-with-vitamin-c-quercetin-administration
 
https://www.suzannegazdamd.com/blog/food-for-thought-and-brain-health
 
https://www.suzannegazdamd.com/blog/new-study-finds-that-dietary-flavonoids-could-help-maintain-cognitive-function
 
References:
 
Harvard Health Publishing
https://www.health.harvard.edu/mind-and-mood/the-thinking-on-flavonoids
 
Zhang, HW., Hu, JJ., Fu, RQ. et al. Flavonoids inhibit cell proliferation and induce apoptosis and autophagy through downregulation of PI3Kγ mediated PI3K/AKT/mTOR/p70S6K/ULK signaling pathway in human breast cancer cells. Sci Rep 8, 11255 (2018). https://doi.org/10.1038/s41598-018-29308-7
 
Harvard T.H. Chan School of Public Health
https://www.hsph.harvard.edu/nutritionsource/food-features/tea/
 
Rizwan, A., Zinchenko, A., Özdem, C. et al. The effect of black tea on human cognitive performance in a cognitive test battery. Clin Phytosci 3, 13 (2017). https://doi.org/10.1186/s40816-017-0049-4
 
Pervin M, Unno K, Nakagawa A, et al. Blood brain barrier permeability of (-)-epigallocatechin gallate, its proliferation-enhancing activity of human neuroblastoma SH-SY5Y cells, and its preventive effect on age-related cognitive dysfunction in mice. Biochem Biophys Rep. 2017;9:180-186. Published 2017 Jan 5. doi:10.1016/j.bbrep.2016.12.012
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5614586/
Pervin M, Unno K, Takagaki A, Isemura M, Nakamura Y. Function of Green Tea Catechins in the Brain: Epigallocatechin Gallate and its Metabolites. International Journal of Molecular Sciences. 2019; 20(15):3630. https://doi.org/10.3390/ijms20153630
 
Yongjie Li, Sibai Zhou, Jinze Li, Yuhua Sun, Hamlati Hasimu, Rui Liu, Tiantai Zhang.
Quercetin protects human brain microvascular endothelial cells from fibrillar β-amyloid1–40-induced toxicity. Acta Pharmaceutica Sinica B. Volume 5, Issue 1, 2015, Pages 47-54,
ISSN 2211-3835. https://doi.org/10.1016/j.apsb.2014.12.003.
https://www.sciencedirect.com/science/article/pii/S2211383514001245
 
Science Direct - Flavanol
https://www.sciencedirect.com/topics/chemistry/flavonol
 
Chen AY, Chen YC. A review of the dietary flavonoid, kaempferol on human health and cancer chemoprevention. Food Chem. 2013;138(4):2099-2107. doi:10.1016/j.foodchem.2012.11.139
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3601579/
 
Dabeek WM, Marra MV. Dietary Quercetin and Kaempferol: Bioavailability and Potential Cardiovascular-Related Bioactivity in Humans. Nutrients. 2019;11(10):2288. Published 2019 Sep 25. doi:10.3390/nu11102288
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6835347/#:~:text=The%20richest%20plant%20sources%20of,kaempferol%2C%20respectively%20%5B17%5D.
 
Science Direct – Chemistry
https://www.sciencedirect.com/topics/chemistry/myricetin
 
Jo, K.W., Lee, D., Cha, D.G. et al. Gossypetin ameliorates 5xFAD spatial learning and memory through enhanced phagocytosis against Aβ. Alz Res Therapy 14, 158 (2022). https://doi.org/10.1186/s13195-022-01096-3
 
North Carolina State Extension
https://plants.ces.ncsu.edu/plants/hibiscus-sabdariffa/
 
Agrawal, P., Agrawal, C., Blunden, G. Pharmacological Significance of Hesperidin and Hesperetin, Two Citrus Flavonoids, as Promising Antiviral Compounds for Prophylaxis Against and Combating COVID-19. Sage Pub. (2021) https://journals.sagepub.com/doi/pdf/10.1177/1934578X211042540
 
Benameur T, Giacomucci G, Panaro MA, et al. New Promising Therapeutic Avenues of Curcumin in Brain Diseases. Molecules. 2021;27(1):236. Published 2021 Dec 31. doi:10.3390/molecules27010236. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8746812/
 
Parachikova, A., Green, K., Hendrix, C., LaFerla, F. Formulation of a Medical Food Cocktail for Alzheimer's Disease: Beneficial Effects on Cognition and Neuropathology in a Mouse Model of the Disease. PLOS One. 2010. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0014015
 
Yongjie Li, Sibai Zhou, Jinze Li, Yuhua Sun, Hamlati Hasimu, Rui Liu, Tiantai Zhang,
Quercetin protects human brain microvascular endothelial cells from fibrillar β-amyloid1–40-induced toxicity, Acta Pharmaceutica Sinica B, Volume 5, Issue 1, 2015, Pages 47-54,
ISSN 2211-3835, https://doi.org/10.1016/j.apsb.2014.12.003.
https://www.sciencedirect.com/science/article/pii/S2211383514001245
 
Askarizadeh A, Barreto GE, Henney NC, Majeed M, Sahebkar A. Neuroprotection by curcumin: A review on brain delivery strategies. Int J Pharm. 2020;585:119476. doi:10.1016/j.ijpharm.2020.119476. https://pubmed.ncbi.nlm.nih.gov/32473377/
 
Aman Khanna, Syam Das S, R. Kannan, Andrew G. Swick, Cristina Matthewman, Balu Maliakel, Sibi P. Ittiyavirah & I. M. Krishnakumar (2022) The effects of oral administration of curcumin–galactomannan complex on brain waves are consistent with brain penetration: a randomized, double-blinded, placebo-controlled pilot study, Nutritional Neuroscience, 25:6, 1240-1249, DOI: 10.1080/1028415X.2020.1853410
 
More about CurQfen
https://www.curqfen.net/
 
Manna J, Dunbar GL, Maiti P. Curcugreen Treatment Prevented Splenomegaly and Other Peripheral Organ Abnormalities in 3xTg and 5xFAD Mouse Models of Alzheimer’s Disease. Antioxidants. 2021; 10(6):899. https://doi.org/10.3390/antiox10060899
 
Calapai G, Bonina F, Bonina A, et al. A Randomized, Double-Blinded, Clinical Trial on Effects of a Vitis vinifera Extract on Cognitive Function in Healthy Older Adults. Front Pharmacol. 2017;8:776. Published 2017 Oct 31. doi:10.3389/fphar.2017.00776
https://pubmed.ncbi.nlm.nih.gov/29163162/
 
Halil Ibrahim Guler, Fulya Ay Sal, Zehra Can, et al. Targeting CoV-2 Spike RBD and ACE-2 Interaction with Flavonoids of Anatolian Propolis by in silico and in vitro Studies in terms of possible COVID-19 therapeutics. bioRxiv. 2021. https://www.biorxiv.org/content/10.1101/2021.02.22.432207v2.full
 
Yongjie Li, Sibai Zhou, Jinze Li, Yuhua Sun, Hamlati Hasimu, Rui Liu, Tiantai Zhang,
Quercetin protects human brain microvascular endothelial cells from fibrillar β-amyloid1–40-induced toxicity, Acta Pharmaceutica Sinica B, Volume 5, Issue 1, 2015, Pages 47-54, ISSN 2211-3835. https://doi.org/10.1016/j.apsb.2014.12.003.
 
De Luca P, Camaioni A, Marra P, et al. Effect of Ultra-Micronized Palmitoylethanolamide and Luteolin on Olfaction and Memory in Patients with Long COVID: Results of a Longitudinal Study. Cells. 2022;11(16):2552. Published 2022 Aug 17. doi:10.3390/cells11162552
 
Mirica® - pure Levagen® Palmitoylethanolamide (PEA)
https://youngnutra.com/
 
Kaul R, Paul P, Kumar S, Büsselberg D, Dwivedi VD, Chaari A. Promising Antiviral Activities of Natural Flavonoids against SARS-CoV-2 Targets: Systematic Review. International Journal of Molecular Sciences. 2021; 22(20):11069. https://doi.org/10.3390/ijms222011069
 
Hoai Thi Thu Tran, Nguyen Phan Khoi Le, et al. Common dandelion (Taraxacum officinale) efficiently blocks the interaction between ACE2 cell surface receptor and SARS-CoV-2 spike protein D614, mutants D614G, N501Y, K417N and E484K in vitro. bioRxiv. 2021. https://www.biorxiv.org/content/10.1101/2021.03.19.435959v1
Tito A, Colantuono A, Pirone L, Pedone E, Intartaglia D, Giamundo G, Conte I, Vitaglione P and Apone F (2021) Pomegranate Peel Extract as an Inhibitor of SARS-CoV-2 Spike Binding to Human ACE2 Receptor (in vitro): A Promising Source of Novel Antiviral Drugs. Front. Chem. 9:638187. doi: 10.3389/fchem.2021.638187
 
Additional sources:
 
Ayaz M, Sadiq A, Junaid M, Ullah F, Ovais M, Ullah I, Ahmed J and Shahid M (2019) Flavonoids as Prospective Neuroprotectants and Their Therapeutic Propensity in Aging Associated Neurological Disorders. Front. Aging Neurosci. 11:155. doi: 10.3389/fnagi.2019.00155
https://www.frontiersin.org/articles/10.3389/fnagi.2019.00155/full
 
Jo, K.W., Lee, D., Cha, D.G. et al. Gossypetin ameliorates 5xFAD spatial learning and memory through enhanced phagocytosis against Aβ. Alz Res Therapy 14, 158 (2022). https://doi.org/10.1186/s13195-022-01096-3
 
American Academy of Neurology. (2022, November 22). Antioxidant flavonols linked to slower memory decline: Fruits, vegetables, tea may be helpful. ScienceDaily. Retrieved December 18, 2022 from www.sciencedaily.com/releases/2022/11/221122221308.htm
 
Devi S, Kumar V, Singh SK, Dubey AK, Kim JJ. Flavonoids: Potential Candidates for the Treatment of Neurodegenerative Disorders. Biomedicines. 2021;9(2):99. Published 2021 Jan 20. doi:10.3390/biomedicines9020099
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909525/

In recent weeks, there have been even more study findings that highlight the importance of dietary influences and the effects on cognitive health. ​

In recent weeks, there have been even more study findings that highlight the importance of dietary influences and the effects on cognitive health. We know we are in the midst of a tremendous rise of neurodegenerative diseases such as Alzheimer’s, Parkinson’s disease, amyotrophic lateral sclerosis (ALS), Huntington’s disease, and other often serious conditions. Although clinical presentations vary with each disease, they all share a common thread of “cellular stress response,” which includes neuroinflammation, oxidative stress, proteotoxicity, and endoplasmic reticulum (ER)-stress. So, what are the potential causes and how can we combat this situation to better protect our brain health?
 
Additionally, there are numerous other factors, such as the increasing toxicity of our environment caused by the use of heavy metals, pesticides, chemicals, and more, that all have contributed to a surge in the number of patients with neurodegenerative disease. Since many brain-related disorders strike primarily in mid- to late-life, the incidence was expected to soar as the population ages, so even before COVID we anticipated a likely rise in the incidence of these conditions. But, the numbers are extremely concerning for clinicians and patients alike.
In fact, one of my latest blogs looks closely at the current data and questions whether we may indeed have a new form of Alzheimer’s with which to contend.
 
Commensurately, other research has shown findings have shown a close correlation between COVID-19 and neurodegenerative characteristics bringing the potential role of COVID-19 in the future development of neurodegenerative diseases into the spotlight.  Lingering viral fragments and in particular spike protein are driving many of the pathological mechanisms that may impact the development of these illnesses; note that spike protein may linger both post infection and post vaccine.
 
“Intellectual” nourishment: a closer look at flavonoids.
 
But, there are things we can do to counter some of these negative factors. A recently published article describes the value of flavonoids, which are readily available, naturally occurring phytonutrients found in abundance in fruits and vegetables, and have been well documented for various health-promoting effects. You also may be familiar with flavonols, which are simply a subclass of the flavonoid family of phytonutrients.
 
Flavonoids exert multiple neuroprotective actions within the brain, such as protection of neurons from neurotoxins and suppression of neuron-inflammation, thereby improving memory, learning, and overall cognitive function. 
 
The study, “Association of Dietary Intake of Flavonols with Changes in Global Cognition and Several Cognitive Abilities,” was conducted using 961 participants (60-100 years) of the Rush Memory and Aging Project, which is a prospective cohort of community-dwelling Chicagoans of retirement communities and senior public housing who were followed by researchers for an average of 6.9 years.
 
The average age of subjects was 81 with no signs of dementia. Each patient was asked to complete a food questionnaire each year for seven years. In addition, the participants underwent annual cognitive and memory tests and were quizzed on their time spent being physically and mentally active. People were divided into groups based on their daily intake of flavonols. The lowest intake was about 5 milligrams a day; the highest 15 milligrams a day — equal to about a cup of dark leafy greens. For comparison, the average flavonol intake in US adults is about 16 to 20 milligrams per day, according to the study.
 
The study looked at the impact of the four major flavonols — kaempferol, quercetin, myricetin, and isorhamnetin — on the rate of cognitive decline over the seven year period. While scientists found no positive effect with dietary isorhamnetin, the other three flavonols did show significant promise. 
 
The greatest impact was found with kaempferol: people who ate the highest amounts of foods with kaempferol showed a 0.4 units per decade slower rate of cognitive decline compared with those who ate the fewest, according to the study.  
 
Good sources of kaempferol are:

• Onions, asparagus and berries
• Richest plant sources are spinach, kale and other green leafy vegetables
• Herbs such as chives, dill and tarragon

 
Next up was myricetin; people who consumed the most foods with myricetin had a 0.3 units per decade slower rate of cognitive decline compared with the lowest consuming group. Good sources include:

• Spinach and strawberries contain high levels of myricetin, but
• Honey, black currants, grapes and other fruits and berries
• Vegetables, nuts, and tea

 
People who ate the most foods with quercetin showed a 0.2 units per decade slower rate of cognitive decline. Good dietary sources are:

• Onions, which contain the highest levels
• Broccoli, cauliflower, curly kale, leeks, spinach
• Blueberries and strawberries

 
The results of this study suggest that “dietary intakes of total flavonoids constituents may be associated with slower decline in global cognition and multiple cognitive abilities with older age.”
 
The USDA provides a helpful chart that features the flavonoid content of many fruits and vegetables at: https://www.ars.usda.gov/ARSUserFiles/80400525/Articles/AICR03_VegFlav.pd

More research points to more reasons to eat well for our brain’s sake!
 
We have previously written about the role of flavonoids and studies that attest to their value in cognitive health. And in other recent research conducted with nearly 11,000 subjects of the Brazilian Longitudinal Study of Adult Health, findings noted that higher consumption of ultra-processed foods was associated with a higher rate of global and executive function decline after a median follow-up of eight years. Ultra-processed food, like chips, microwave meals, many breakfast cereals, candy, soft drinks, and more, really should be called “thoughtless food” because of its potentially negative effect on our thinking abilities.
 
Food really is medicine! So, while we know that in our very busy lives it can be hard to totally avoid eating convenience foods, it’s truly important that we try to choose whole, fresh food whenever possible to give our bodies and our brains the very best chance at optimal health.
Remember the wise words of Hippocrates who said “let food be thy medicine, and let medicine be thy food.” If you have questions regarding dietary options that are suitable for your particular needs be sure to consult your physician or nutritionist for guidance. And please check back soon for our follow-up blog that will look at flavonoids in even more detail!
 
In hope and healing,
Dr. Suzanne Gazda

References:
 
Gazda, S. Do we have a new form of Alzheimer’s disease in the making? (2022)
https://www.suzannegazdamd.com/blog---long-covid/do-we-have-a-new-form-of-alzheimers-disease-in-the-making
 
Li, C., Liu, J., Lin, J. et al. COVID-19 and risk of neurodegenerative disorders: A Mendelian randomization study. Transl Psychiatry 12, 283 (2022). https://doi.org/10.1038/s41398-022-02052-3
 
Holland, Thomas Monroe et al "Association of Dietary Intake of Flavonols With Changes in Global Cognition and Several Cognitive Abilities." Neurology (2022): 10.1212/WNL.0000000000201541. Web. 08 Dec. 2022.

Findings link moderate use to an increase in strokes in young people
​
A recent study has certainly raised additional concerns regarding consuming alcohol beverages and our neurological health, particularly in regard to young adults.

Now, researchers have published findings that indicate young people considered “moderate to heavy drinkers” were more likely to have a stroke compared with those who were light drinkers or didn’t drink any alcohol at all. The more than 1.5 million subjects were in their 20s and 30s and part of a Korean national health database.
 
So, the question of “how much is too much” is definitely something we need to further explore for the benefit of our brains AND to ensure the current and future health of our youth!
 
More than 90% of the stroke burden is attributable to modifiable risk factors like drinking.

Alcohol consumption is a modifiable, lifestyle risk factor, meaning it’s something we actually can control to potentially reduce disease occurrence. Other modifiable risks include diet and avoiding processed foods, getting exercise, quitting or never smoking, and getting adequate sleep.

Understanding the data can inform better decision making.
 
So, how do you think you did on the questions above? The answers are: B, C, B. 
 
If you were unsure of the correct responses, it’s crucial to become aware of the facts regarding alcohol consumption and how all ages can be adversely affected. And the recent study linking increased stroke incidence to drinking habits in our youth population puts the spotlight on why we must address this topic right now.
 
College alcoholism affects millions of primarily college-aged students every year, although we know many children are drinking at even younger ages. According to the Centers for Disease Control and Prevention (CDC), roughly 80% of college students – four out of every five – consume alcohol to some degree. And it’s estimated that 50% of those students engage in binge drinking, which involves consuming too much alcohol in too little time.
 
About 1 in 5 deaths of people ages 20 to 49 were attributable to excessive alcohol use in the United States, according to another recent study; for people ages 20 to 64, drinking-related deaths accounted for 1 in 8.
 
The CDC defines moderate drinking as two drinks or less in a day for men or one drink or less in a day for women. And two-thirds of all adults report drinking MORE than moderate amounts at least once a month.
 
The CDC also estimates that 1 in 6 adults binge drink.  Binge drinking is defined as four or more drinks on an occasion for a woman, and five or more drinks for a man — with a quarter of these adults doing so at least weekly. 
 
Mechanisms of stroke and alcohol.
 
Several possible mechanisms may explain the relationship between alcohol consumption and stroke. First, excessive and/or regular alcohol consumption can lead to hypertension or high blood pressure, which we know increases our risk of stroke.
 
Alcohol increases the incidence of atrial fibrillation (AF) in a dose-dependent manner, and the risk for thromboembolism; cerebral vasospasm has been reported as a possible mechanism as well. A report in Neurologyconcluded: young adults who engaged in moderate to heavy drinking demonstrated a higher risk for incident stroke, especially hemorrhagic stroke. Reducing alcohol consumption should be emphasized in young adults with heavy drinking habits as part of any stroke prevention strategy.
 
What the study shows re: increased strokes in young consumers of alcohol.
 
This latest report found that people in their 20s and 30s who drink moderate to heavy amounts of alcohol may be more likely to have a stroke as young adults than people who drink low amounts or no alcohol at all.
 
According to the Korean study, the risk of stroke increased commensurate with the number of years that people reported moderate or heavy drinking. 

Those who drank 105 grams (equal to roughly 1.5 ounces) or more of alcohol per day each week were considered to be moderate or heavy drinkers - and just 1.5 ounces is considered as one drink. A standard drink contains about 14 grams of alcohol, which is equivalent to 12 ounces of beer, five ounces of wine or 1.5 ounces of liquor.
 
Of the more than 1.5 million young people included in the study (both men and women), a total of 3,153 suffered a stroke during the study. People who were moderate to heavy drinkers for two or more years of the study were more likely to have a stroke than people who were light drinkers or did not drink alcohol.
 
And as the number of years of moderate to heavy drinking increased, so did the risk of stroke. People with two years of moderate to heavy drinking had an approximate 19% increased risk, people with three years had a 22% increased risk, and those with four years had a 23% increased risk of having a stroke.

These results were determined after researchers accounted for other factors that could affect the risk of stroke, such as high blood pressure, smoking and body mass index. The association was mainly due to an increased risk of hemorrhagic stroke, or a type of stroke caused by bleeding in the brain.
 
This research supports previous findings, one of which was a study that linked even low levels of alcohol consumption with increased blood pressure that can lead to strokes.
 
Alcohol and other neurological concerns.
 
Youth who are identified as heavy drinkers exhibited a steeper decline in frontal gray matter volume, with evidence of neurotoxicity noted in the brain’s white matter. Previous investigations also have found that alcohol significantly impairs learning and memory in teens. And compounding concerns is the rate of deaths of nearly 30% directly attributed to the rise in alcohol consumption in the U.S. in just the first year of the pandemic, according to additional data from the CDC. 
 
The situation demands more communication and education regarding the risks to young people associated with drinking excessively and in amounts they may not even realize could endanger their neurological wellbeing. It’s unlikely that a 25-year-old will consider the possibility that their daily beer or glass of wine could lead to something as potentially devastating as a stroke. The goal is not to frighten our children or youth, but to fully communicate all the facts so they have the opportunity to make informed lifestyle choices for their own current and future health. And as always, be sure to talk to your family clinician for resources and recommendations – we are all here to help!
 
In hope and healing,
Dr. Suzanne Gazda
 
Other related reading from our blog library:
 
https://www.suzannegazdamd.com/blog/it-shouldnt-take-a-pandemic-for-us-to-take-a-long-look-at-our-health-trends
 
https://www.suzannegazdamd.com/blog/stroke-and-covid-19
 
https://www.suzannegazdamd.com/blog/oxygen-and-sleep-what-your-brain-needs-to-know
 
References:
 
Jae-wook Chung, So-Ryoung Lee et al. Cumulative Alcohol Consumption Burden and the Risk of Stroke in Young Adults: A Nationwide Population-Based Study. Neurology. Nov 2022. https://n.neurology.org/content/neurology/early/2022/11/02/WNL.0000000000201473.full.pdf
 
Centers for Disease Control and Prevention (CDC), Alcohol and Public Health
https://www.cdc.gov/alcohol/fact-sheets/moderate-drinking.htm
 
Esser MB, Leung G, Sherk A, et al. Estimated Deaths Attributable to Excessive Alcohol Use Among US Adults Aged 20 to 64 Years, 2015 to 2019. JAMA Netw Open. 2022;5(11):e2239485. doi:10.1001/jamanetworkopen.2022.39485
 
Iona Y Millwood, Robin G Walters, Xue W Mei, et al. Conventional and genetic evidence on alcohol and vascular disease aetiology: a prospective study of 500 000 men and women in China. The Lancet. Volume 393, ISSUE 10183, P1831-1842, May 04, 2019. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31772-0/fulltext
 
Tapert SF, Eberson-Shumate S. Alcohol and the Adolescent Brain: What We've Learned and Where the Data Are Taking Us. Alcohol Res. 2022;42(1):07. Published 2022 Apr 7. doi:10.35946/arcr.v42.1.07. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8999519/
 
Silveri MM. Adolescent brain development and underage drinking in the United States: identifying risks of alcohol use in college populations. Harv Rev Psychiatry. 2012;20(4):189-200. doi:10.3109/10673229.2012.714642. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4669962/

In a recent study, researchers made these concerns abundantly clear, having examined the harmful effects to the brain relevant to glyphosate, which is the active ingredient in many commercial herbicides and the most widely used herbicide worldwide (frequently marketed under the brand name Roundup).
 
The results of this study show for the first time that glyphosate does in fact infiltrate the brain, easily crossing the blood-brain barrier (BBB), and elevating both the expression of TNFα and soluble Aβ. This is shown to disrupt the transcriptome, which is the protein-coding part of an organism's genome, in a dose-dependent manner and suggests that exposure to this herbicide may have detrimental outcomes regarding the health of the general population. 
 
Aberrant TNFα signaling has been implicated in numerous pathological conditions, including cancer, rheumatoid arthritis, psoriasis, and multiple sclerosis, as well as immune, inflammatory, and neurodegenerative diseases such as Alzheimer’s. As the study authors noted, “the recent rise in glyphosate application to corn and soy crops correlates positively with increased death rates due to Alzheimer’s disease and other neurodegenerative disorders.”
 
There are many other perspectives regarding the deleterious impacts to our brain health that also correspond to this recent research. From her book, Toxic Legacy: How the Weedkiller Glyphosate Is Destroying Our Health and the Environment, Dr. Stephanie Seneff wrote, “Glyphosate is the active ingredient in the pervasive weedkiller Roundup. It is the most widely-used herbicide in the world, and the United States uses more per capita than any other country. The United States also faces a healthcare crisis with alarmingly rising rates of diabetes, obesity, autism, Alzheimer’s, infertility and cancer.  In this talk, I will argue that glyphosate is a primary factor in the declining health of our population. I will also provide evidence that glyphosate is disrupting the entire ecosystem, from water fleas to bees to deer, pigs and humans. I propose a unique mechanism of toxicity of glyphosate based on its effects as an amino acid analogue of glycine."
 
You can also refer to our blog archives for additional related reading, including:
 
https://www.suzannegazdamd.com/scientifically-speaking1/neuro-degenerative-disease-and-toxins
 
https://www.suzannegazdamd.com/blog/is-there-more-to-immune-mediated-dysfunction-in-even-more-neurological-disorders
 
https://www.suzannegazdamd.com/blog/what-how-we-eat-now-could-determine-our-future-brain-health
 
https://www.suzannegazdamd.com/blog/the-immune-response-its-more-important-than-ever-to-ready-our-defenses
 
https://www.suzannegazdamd.com/blog/our-childrens-pandemic-of-neuro-immune-disorders
 
It is vital, if accessible and available, to choose organic and non-GMO products and produce whenever possible…your health and the future health of your children truly depend on it. For more information or if you have questions, please reach out to our office – we’re here to help!
 
In health and hope,
Dr. Suzanne Gazda
 
References:
 
Winstone et al. Glyphosate infiltrates the brain and increases pro-inflammatory cytokine TNFα: implications for neurodegenerative disorders. Journal of Neuroinflammation (2022) 19:193
https://doi.org/10.1186/s12974-022-0254
https://jneuroinflammation.biomedcentral.com/track/pdf/10.1186/s12974-022-02544-5.pdf
 
Seneff, S. Toxic Legacy: How the Weedkiller Glyphosate Is Destroying Our Health and the Environment. July 2021.https://www.amazon.com/Toxic-Legacy-Weedkiller-Glyphosate-Environment/dp/1603589295

And as our lifestyles and eating habits have shifted over the years away from freshly made meals at home to fast food and takeaway items, so have the issues resulting from these changes contributed to numerous health issues in all age groups.
 
Now, a recent study published in the journal, Alzheimer’s & Dementia, show a commensurate link to the rates of dementia occurring in our later years that was reflected by cholesterol levels at age 35, specifically our high density lipoproteins (HDL) and blood glucose levels.
 
Specifically, scientists looked for an association as to whether vascular and metabolic diseases measured in early adulthood are associated with Alzheimer's disease (AD) later in life. Using data from the longtime Framingham Heart Study, they found that:
 

• A 15 mg/dL increase in high-density lipoprotein (HDL) cholesterol was associated with decreased AD risk during early (15.4%, P = 0.041) and middle (17.9%, P = 0.014) adulthood. 
• A 15 mg/dL increase in glucose measured during middle adulthood was associated with 14.5% increased AD risk (P = 0.00029). These findings remained significant after adjusting for treatment.
• Triglyceride levels were associated with Alzheimer's only in the early adulthood group. Findings remained significant after adjusting for treatment.
• Blood glucose in middle adulthood was associated with Alzheimer's dementia per 15 mg/dL increase.
• The findings show that while we have long-known cholesterol and glucose measured in blood profiles point to an increased risk of Alzheimer’s dementia, this study is significant in its results that identify the occurrence beginning at much younger ages.1

 
What your blood profile measures.
HDL cholesterol is often referred to as our “good” cholesterol as it carries cholesterol from other parts of your body back to your liver where the liver can then remove it from your body. Conversely, low-density lipoproteins, or “bad” cholesterol, can lead to a buildup of cholesterol in your arteries that is tied to cardiovascular disease and strokes.2
 
Total cholesterol numbers reflect both HDL and LDL numbers as well as triglycerides, which are not a type of cholesterol but are included in your lipoprotein blood profile. Triglycerides are the most common type of fat found in our body and are stored until we need to use them; however, high triglycerides typically are found along with high HDL and identified in conditions such as diabetes and metabolic syndrome. 

How can we address the risk factors now?
 
The study authors concluded that ‘"Intervention targeting cholesterol and glucose management starting in early adulthood can help maximize cognitive health in later life.” What this means is taking a healthy approach to our diets along with addressing modifiable risk factors, such as smoking cessation and giving up sedentary lifestyles in favor of more exercise. We must also look at the tenets of the Bredesen Protocol® to Alzheimer’s treatment, and one that we utilize in our practice, that is founded upon a comprehensive lifestyle and nutritional approach designed to reverse the cognitive decline of Alzheimer’s and related disorders, and prevent Alzheimer’s for those at risk. Additionally, it’s critical whenever possible to eat only non-GMO foods or products that haven’t been genetically modified in a way that does not occur naturally. There are several studies that show how GMO-containing foods may act as an environmental toxin in our system and actually alter our gut microbiome, which plays a key role in our health and affects such processes as metabolism and our immune system regulation. An impacted microbiome could then lead to the development of diseases including Alzheimer’s and Parkinson’s.3
 
Our blog library has several articles that look at the issues of high cholesterol, obesity, and other factors that are linked to incidence of dementia and other neurodegenerative disease:
 
Dementia and vascular inflammation
https://www.suzannegazdamd.com/blog/vascular-and-inflammatory-markers-of-dementia
 
Addressing lipid markers
https://www.suzannegazdamd.com/blog/addressing-lipid-markers-may-be-an-approach-to-brain-health
 
Alzheimer’s as an autoimmune disease.
https://www.suzannegazdamd.com/blog/is-alzheimers-an-autoimmune-disease
 
Is Alzheimer’s preventable?
https://www.suzannegazdamd.com/blog/what-if-alzheimers-is-preventable
 
The prognosis for our youth’s health and our own medical futures can be significantly improved if take steps right NOW to change how and what we eat. We know, it’s not easy. But, if we are to enhance the potential outcome for the wellbeing of our neurological processes, it’s definitely an effort worth making. Let us know how we can help!
 
In hope and healing,
Dr. Suzanne Gazda
 
References:
 
1 Zhang, X, Tong, T, Chang, A, et al. Midlife lipid and glucose levels are associated with Alzheimer's disease. Alzheimer's Dement. 2022; 1- 13. https://doi.org/10.1002/alz.12641
 
2 The American Heart Association
https://www.heart.org/en/health-topics/cholesterol/about-cholesterol/what-your-cholesterol-levels-mean
 
3 Wang, H., Yang, F., Zhang, S. et al. Genetic and environmental factors in Alzheimer’s and Parkinson’s diseases and promising therapeutic intervention via fecal microbiota transplantation. npj Parkinsons Dis. 7, 70 (2021). https://doi.org/10.1038/s41531-021-00213-73

Sleep issues? Take action now!
 
Quality sleep – we know, you’ve often heard us talk about how important it is! Now, even more research has captured our attention about the need for promptly addressing any concerns.

Scientists in examining data from over 1,400 participants in the Rush Memory and Aging Project found that there may be a “bidirectional relationship” between excessive daytime napping and dementia.1 The Rush Memory and Aging Project was initiated in 1997 to “to identify factors associated with the maintenance of cognitive health despite the accumulation of AD (Alzheimer’s disease) and other pathology.”
 
The review’s authors noted several key points in the methodology and findings:

• Older adults tend to nap more often and for longer periods of time
• The progression of Alzheimer's dementia accelerates this change, more than doubling the annual increases in nap duration and frequency
• Longer, more frequent daytime naps were associated with a higher risk of Alzheimer's dementia
• More excessive (longer and/or more frequent) daytime napping also was correlated with worse cognition a year later - and worse cognition was correlated with more excessive naps a year later.

 
Thus, it would appear that there is some bidirectional relationship and common pathophysiology that exists between excessive napping and dementia. Additional research is certainly needed in order to better understand the relationship in developing interventions.
 
“Why am I so tired?!”
 
Certainly, our history of overwhelmed lifestyles has impacted the quality of sleep for almost all people, even in the absence of an identified health condition. Stress, lack of exercise, poor dietary choices, overuse of technology devices especially at night, and other factors contribute to negative sleep patterns. 
 
Sleep apnea and sleep-disordered breathing, discussed in detail in our previous blog, can put our brains at risk for Alzheimer’s and other neurological impairments. From decreased vascular supply to a reduction in gray matter, sleep disorders are nothing to ignore! Even if you think you’re sleeping an ample number of hours, you may not actually be getting true quality rest if your natural sleep cycles are constantly disturbed by the effects of apnea or disordered breathing. And you don’t necessarily need to have one of these or another specific condition – turning and tossing all night, repeated waking from too much caffeine late in the day or a heavy meal right before bedtime can all rob you of a sound night’s slumber.
 
Don’t let your concerns about fatigue and poor sleep keep you up at night – talk to your physician for ways to combat the problem with appropriate therapies, meditation, and more. And give your brain the beauty sleep it needs to stay healthy and happy!
 
In hope and healing,
Dr. Suzanne Gazda 
 
References and additional reading:
 
1 Li, P, Gao, L, Yu, L, et al. Daytime napping and Alzheimer's dementia: A potential bidirectional relationship. Alzheimer's Dement. 2022; 1– 11. https://doi.org/10.1002/alz.12636
 
https://www.suzannegazdamd.com/blog/oxygen-and-sleep-what-your-brain-needs-to-know
 
https://www.suzannegazdamd.com/blog/your-brains-wellbeing-starts-with-sleeping-well
 
https://www.suzannegazdamd.com/blog/a-well-spent-day-brings-happy-sleep-leonardo-da-vinci

So, why would we wait to employ the most effective means available to quickly tamp down immune dysregulation and subsequent inflammation that drives virtually every disorder including PANS and PANDAS?
 
PANS or pediatric acute-onset neuropsychiatric syndrome and PANDAS, pediatric autoimmune neuropsychiatric disorder associated with streptococcus infection, can occur when our immune system, in mistaking normal cells for infectious agents, essentially launches an attack on our own tissues. The resulting impacts, which may develop very swiftly, can include obsessive compulsive disorder (OCD), motor tics, behavioral changes, eating disorders, and many other serious and often life-changing symptoms. It’s important to note too that while many PANS and PANDAS patients are between the ages of 3 and 13 years, there are instances where children (and young adults) outside that range have been affected.1 
 
But according to new data presented at the IgNS 2021 Conference “timely treatment with IV immunoglobulin (IVIG) therapy can help children who develop obsessive-compulsive disorder (OCD) and other severe psychiatric or neurologic symptoms in the aftermath of streptococcal or other infections.”
 
The key word here is TIMELY. And, as anyone involved in the care of PANS and PANDAS patients knows, there unfortunately can be significant delays in not only getting an accurate diagnosis, but also obtaining appropriate treatment. The disorders are often mistaken for other illnesses or patients initially may be seen by practitioners who just aren’t as familiar with these very complex disorders. Subsequently, the right therapies that could potentially help ward off more serious complications may not be employed from the start and this ultimately exacerbates the disease progression.
 
A recent article discussed the IgNS 2021 conference findings and offered insight from several physicians and researchers at prominent universities and medical centers that clearly stress the need for expedited care. Dr. Sydney Rice, University of Arizona (UA)/Banner Health Children’s Postinfectious Autoimmune Encephalopathy (CPAE) Center of Excellence - Tucson, cited the promising results from the use of IVIG as shown by Stanford University researchers, something with which Dr. Michael Daines, MD, an associate professor of pediatric allergy and immunology at the UA College of Medicine and the other CPAE Center co-director, concurred. 
 
Dr. Rice explained too that while the use of other therapies such as antibiotics and anti-inflammatories can help, they also may over-suppress the immune system. The multi-modality mechanisms of IVIG works to block the production of the antibodies that are at the root of the disorders, “so we use (it) in immunomodulatory doses to try to stop these antibodies from doing what they do.”
 
However, and something to which parents and clinicians can attest, getting IVIG approved by insurance providers is no easy task. The current costs for these treatments exceeds the costs for generic antibiotics or traditional anti-inflammatory therapies so it can be a long-waged challenge to obtain approval for something so many patients desperately need…at the expense of their health and prognosis.
 
There is no single or simple solution, but the message is clear – the sooner we put the out the fire and provide the RIGHT treatment for those affected by PANS, PANDAS, and other related auto-encephalopathy conditions, the sooner we can hope to see improvement and resolution of symptoms. 
 
The cost of delaying assessment and treatment is to our children’s futures – we must continue to work together toward making IVIG and other appropriate therapies more accessible and more quickly available! 
 
In hope and healing,
Dr. Suzanne Gazda 
 
To learn more about IVIG in PANS and PANDAS see: 
https://www.suzannegazdamd.com/blog/new-study-further-supports-benefits-of-ivig-treatment-in-pans-patients
 
For related resources and support groups, please see our Helpful Links section on our website.
 
You’ll also find numerous articles about PANS and PANDAS in our blog library; just use the Search tool on each page to locate more information by keyword and topic.
 
References

1 ASPIRE, Alliance to Solve PANS & Immune-Related Encephalopathies
https://aspire.care/what-is-pans/who-gets-pans/
 
Buckley, B. Pediatric OCD May Respond to Timely IG Therapy. Specialty Pharmacy Continuum® November 16, 2021. https://www.specialtypharmacycontinuum.com/Clinical/Article/11-21/Pediatric-OCD-May-Respond-to-Timely-IG-Therapy/65290

The severity and causes of neuropathy vary and can include diabetes and neurological or autoimmune disorders like lupus or Guillain-Barre syndrome. Unfortunately the single-most common denominator perhaps has been the lack of effective treatment -- there are just very few options available to physicians to provide symptomatic relief through medications or otherwise. And as we are already seeing every day with an increasing number of “long-hauler” post-COVID patients, there is commensurately an even greater need now to find more ways to resolve neuropathic pain associated with all of these conditions. 
 
But what if it was possible to employ a similar protocol used in migraine treatments that addresses this same type of underlying inflammation which we know is present in virtually every condition? And could the neuropathy also be improved?
 
Let’s talk about CGRP inhibitors and macrophages.
 
What do CGRP inhibitors and macrophages have to do with addressing neuropathic pain? First, CGRP or calcitonin gene-related peptide (CGRP) inhibitors are a relatively new class of medications designed to block the effect of CGRP, which is a small protein found in the sensory nerves that supply the head and the neck. CGRP is involved in pain transmission and in the case of migraine, for example, levels increase during an attack. 2
 
Macrophages are cells involved in the detection and destruction of bacteria and other harmful organisms. One of the major components of the inflammatory process, they can play an important role in eliminating diseased and damaged cells through their programmed cell death. As such, macrophages release cytokines, small proteins that signal the immune system to do its job – but the overproduction of these proteins in the presence of an infection, for example, can result in a cytokine storm and severe inflammatory reaction.3
 
Some recent research has shown CGRP inhibitors could be used to down-regulate pro-inflammatory macrophages. In the case of a long-hauler protocol, one element is shifting pro-inflammatory to anti-inflammatory cytokines or macrophages using H1 and H2 blockers. Steroids work the same way, as do non-steroidal anti-inflammatory drugs (NSAIDs) and gabapentin. Also, with intravenous immunoglobulin (IVIG), there are multiple mechanisms that can reduce inflammation in both the brain and system-wide.4

Scientists in Denmark studying patients with diabetes-related peripheral neuropathy (DPN) identified several significant findings that point to the role of inflammation in the resulting peripheral pain. Many factors are known to contribute to neuropathic pain in diabetes, including the release of the neuropeptide substance P (SP) and CGRP from sensory nerve terminals and inflammatory mediators (cytokines) from immune cells. The investigators found that “increased macrophages and increased CGRP-expressing and SP-expressing nerve fibers in the skin of patients with P-DPN may be consistent with a role of the immune system and neuropeptides in driving pain in DPN.”5
 
If inhibiting CGRP offers relief in these instances of diabetic neuropathic pain, could they then also provide relief in other applications? This is a fascinating study and one that does offer more hope to a spectrum of patients suffering with debilitating and ongoing symptoms. And we look forward to seeing additional research that can support the development of more therapies for all those who live with this type of chronic pain.
 
In hope and healing,
Dr. Suzanne Gazda
 
For additional reading about IVIG, please see these and other related articles in our blog archives at:
https://www.suzannegazdamd.com/blog/ivig-in-autoimmune-disease-therapies
 
https://www.suzannegazdamd.com/blog/with-more-potential-uses-for-more-diseases-ivig-gains-enhanced-awareness-for-its-multimodal-properties
 
References:
 
1 Cleveland Clinic, www.clevelandclinic.org
 
2 Mohanty D, Lippmann S. CGRP Inhibitors for Migraine. Innov Clin Neurosci. 2020;17(4-6):39-40.
 
3 Arango Duque G and Descoteaux A (2014) Macrophage cytokines: involvement in immunity and infectious diseases. Front. Immunol. 5:491. doi: 10.3389/fimmu.2014.00491
 
4 Saha C, Kothapalli P, Patil V, ManjunathaReddy GB, Kaveri SV, Bayry J. Intravenous immunoglobulin suppresses the polarization of both classically and alternatively activated macrophages. Hum Vaccin Immunother. 2020;16(2):233-239. doi:10.1080/21645515.2019.1602434
 
5 Sandra Sif Gylfadottir, Mustapha Itani, Alexander Gramm Kristensen, et al. Analysis of Macrophages and Peptidergic Fibers in the Skin of Patients With Painful Diabetic Polyneuropathy. Neurol Neuroimmunol Neuroinflamm Jan 2022, 9 (1) e1111; DOI: 10.1212/NXI.0000000000001111

because there are very real consequences to the mind and the brain from one misplaced kick, a hard hit to the head from a fall or even a ball, and other serious injuries. 
 
Fast forward to 2021 and we certainly have good reason to be concerned about traumatic brain injuries (TBIs) and sports-induced head impacts from soccer. The cohort study, “Association of Field Position and Career Length With Risk of Neurodegenerative Disease in Male Former Professional Soccer Players,” included over 7,600 Scottish former professional soccer players (all males) and more than 23,000 members of the general population as the control group. Individuals were matched by sex, gender, and area socioeconomic status.

​“The Beautiful Game” carries risks we haven’t fully discussed or addressed.
 
You may have heard the famous soccer player, Pele, describe his sport as “the beautiful game.” While certainly its acrobatic, almost-choreographed moves can indeed be a thing of amazing beauty, authors of a recent opinion pieceechoed the grave concerns about the many risks we must further investigate to understand how TBIs sustained in soccer can lead to late-life neurodegenerative disease and dementia.

Authors of the opinion article make a very compelling observation about the cohort study as far as its limitations: “the current study increased sensitivity to neurodegenerative disease by examining all available health records for dementia-associated diagnoses. However, qualifying diagnoses did not include mild cognitive impairment, and thus the study likely underestimated early neurodegenerative changes in both former soccer players and control participants.”2
​
So what becomes most clear is that there are indeed consequences which can develop from playing professional or recreational soccer – but we don’t yet have enough research to fully understand these consequences. And we certainly need to include females in future studies to truly understand how to better protect all genders from adverse neurological events today and in the future. It’s also important to note here that a 2017 study by Northwestern University researchers showed that concussions among female soccer players occur at a higher rate than any other male athletes, and even at that time were on the rise.3 With more young women playing the highly popularized sport now, we can imagine the figures are much greater.
 
If you or your children play soccer regularly, or even on a casual basis, and you have ANY reason to be concerned about a resulting head injury, don’t hesitate to seek medical help at the earliest opportunity. TBIs and concussions can present with a variety of symptoms that include, but are not limited to:

• Headache
• Inability to wake
• Nausea and/or vomiting
• Blurred vision or other vision changes
• Drowsiness, dizziness or grogginess
• Slurred or delayed speech

 
But if it’s appropriate to your health conditions and you’ve consulted your physician, try to pursue an active lifestyle and spend time outdoors for the benefit of your beautiful brain! You’ll find more information at:
 
https://www.suzannegazdamd.com/blog/the-immunological-case-for-staying-active
 
https://www.suzannegazdamd.com/blog/the-integral-neural-connection-between-exercise-and-brain-health
 
https://www.suzannegazdamd.com/blog/the-indoor-generation-is-missing-out-on-vitamin-d
 
In hope and health,
Dr. Suzanne Gazda 
 
References:
 
1 Russell ER, Mackay DF, Stewart K, MacLean JA, Pell JP, Stewart W. Association of Field Position and Career Length With Risk of Neurodegenerative Disease in Male Former Professional Soccer Players. JAMA Neurol. 2021;78(9):1057–1063. doi:10.1001/jamaneurol.2021.2403
 
2 Asken BM, Rabinovici GD. Professional Soccer and Dementia Risk—The Ugly Side of the Beautiful Game. JAMA Neurol. 2021;78(9):1049–1051. doi:10.1001/jamaneurol.2021.2246
 
3 American Academy of Orthopaedic Surgeons. (2017, March 14). Female soccer players suffer the most concussions in high school sports: Study finds significant increase in overall reported concussions since traumatic brain injury laws enacted. ScienceDaily. Retrieved September 14, 2021 from www.sciencedaily.com/releases/2017/03/170314081533.htm

The study included youth between 5 and 17 years with continuous health care coverage and if they had an in-person visit with at least one BMI measure before the pandemic (March 2019-January 2020) and another BMI measure during the pandemic (March 2020-January 2021, with at least one additional BMI after June 16, 2020; youth with complex chronic conditions were excluded. And of course, it’s highly likely that children without access to preventive care or health benefits who weren’t part of this review are reflecting these same concerning gains over the last year and a half.
 
According to the data published on JAMA Network, overweight status or obesity increased among children aged 5-11 from 36.2% to 45.7% during the pandemic, an absolute increase of 8.7% and relative increase of 23.8% compared with the reference period (pre-pandemic). The absolute increase in overweight or obesity was 5.2% among 12- through 15-year-olds (relative increase, 13.4%) and 3.1% (relative increase, 8.3%) among 16- through 17-year-olds. Most of the increase among youths aged 5 through 11 years and 12 through 15 years was attributed to an increase in obesity.
 
The conclusions: significant weight gain occurred during the COVID-19 pandemic among youths in KPSC, especially among the youngest children. These findings, as noted by the reporting group, “if generalizable to the U.S. suggest an increase in pediatric obesity due to the pandemic. Further research is advised to identify interventions as well as possible long-term detriments to children’s health.”
 
Additional research – and concerns - about youth and obesity.
 
As cited by the Centers for Disease Control and Prevention, scientists already had found an increased prevalence of both type 1 and 2 diabetes in children during the years 2001-2017. The recently published data was compiled through an observational, cross-sectional, multicenter study of a mean of 3.47 million youths for each prevalence year from six areas in the United States.2
 
We’ve also written just last year about research linking adolescent obesity and an increased risk of multiple sclerosis (MS). Research led by Queen Mary University of London, U.K. estimated that childhood and adolescent obesity is projected to contribute up to 14 percent of overall risk by the year 2035. The incidence was attributed to modifiable risk factors including BMI. 
 
There are a myriad of articles and scientific studies over the years that show exactly how obesity negatively impacts our immune defense, making our systems more vulnerable to infectious disease. Obesity is associated with significant changes in the resident immune cell composition of adipose tissue, which disrupts the balance between pro-inflammatory and anti-inflammatory immune cells in favor of the former – and of this leads to a state of chronic low-grade inflammation that can subsequently give rise to a host of diseases in addition to neurological disorders like MS.

So what can we do to help our children?
 
Limiting calorie-rich, nutrient-poor snacks and meals is one aspect of a healthy eating strategy. Getting regular physical exercise (ideally as a family), replacing sedentary pastimes (e.g. video games and binge-watching television) with physical activity, getting adequate sleep, and practicing what you preach as far as healthy habits should all be part of your approach. Overly restricting calories or shaming children into losing weight most certainly is not the answer, nor is supporting what are often unrealistic body types our kids see on social media every day. Consulting your pediatrician or family physician for guidance specific to your child’s health or existing conditions should be the first step in achieving a goal of wellness and wellbeing. 

Unfortunately, we know the pandemic also has resulted in financial hardships that impacted access to fresh, whole foods, replacing these with inexpensive processed goods and filling starches, for example, solely out of necessity. Families who are struggling with ways to provide better nutrition for their children should look to local agencies for assistance and review more resources at https://www.cdc.gov/healthyweight/children/index.html.
 
It’s not an easy challenge to overcome, but we must approach obesity today as its own epidemic of sorts if we are to ensure a better prognosis for the health of all children tomorrow.
 
In hope and healing,
Dr. Suzanne Gazda 
 
References and additional reading:
 
Gazda Integrative Neurology
It shouldn’t have taken a pandemic to take a serious look at our health.
https://www.suzannegazdamd.com/blog/it-shouldnt-take-a-pandemic-for-us-to-take-a-long-look-at-our-health-trends
 
1 Woolford SJ, Sidell M, Li X, et al. Changes in Body Mass Index Among Children and Adolescents During the COVID-19 Pandemic. JAMA. Published online August 27, 2021. doi:10.1001/jama.2021.15036
 
2 Lawrence JM, Divers J, Isom S, et al. Trends in Prevalence of Type 1 and Type 2 Diabetes in Children and Adolescents in the US, 2001-2017. JAMA. 2021;326(8):717–727. doi:10.1001/jama.2021.11165

But, the pandemic brought with it many changes to daily life that shifted even more the world of these young patients and their families. 
 
Scientists seeking to explore the impact of lockdown on the clinical course of children with PANS or PANDAS expected that with reduced exposure to certain environmental factors, along with positive parenting strategies, that symptoms might have abated or not worsened. However, during the study’s identified period from April 14 through May 3, 2020, survey results showed quite different results than anticipated…parents completing the online survey actually noted an increase in some existing symptoms as well as the initiation of new issues.1

This study included 108 children, adolescents, and young adults identified through a multicenter PANS/PANDAS research program located in several pediatric departments at universities in Italy. Parents completed a questionnaire consisting of 22 questions divided into four sections comprising: sociodemographic details; observed symptoms; parenting strategies; and multiple choice questions regarding tools or actions that promote a decrease or increase in symptoms.
 
Investigators had hypothesized that “few studies have data on the efficacy of psychotherapeutic treatments because they focus primarily on viral etiology, considering it the sole source of symptom triggering in the flare-ups. Given this premise, it is essential to analyze all factors contributing to symptom exacerbation, including environmental factors and triggering events of social, familial, and educational nature.”
 
However, after analyzing parent responses, the study team found:

• An increase in reported symptoms in 71% of the sample.
• Increased symptoms that were best explained by the presence of sleep disturbances and emotional lability.
• Exacerbation of issues that appeared linked to the onset of new symptoms in children and adolescents with depressed moods and eating problems.
• Equally statistically significant was the factor linked to the effects of pandemic stress, such as the fear of contracting the virus.

In summary, researchers noted that “this preliminary study highlights the importance of studying and investigating the causes of increased symptoms in children with PANDAS/PANS” and that “the importance of managing emotions and problematic behaviors is also highlighted. It has also been found that parents' perception of self-efficacy concerning their educational and caring skills can act against the increase in symptoms.” Additionally, the information obtained from the study was in line with recommendations for current treatment approaches.
 
Many of us can attest to the difficulties of life over the last year and a half even without the added struggles of having a chronic illness. For children and youth whose disorders span a wide range of physical and behavioral issues, the dramatic changes imposed by the pandemic seemed to have magnified their challenges. From isolation and school closures to new home routines, an inability to see family or familiar faces, combined with what may be parental concerns about finances and the virus itself, so much has occurred that could impact any child – and especially children with chronic neurological diagnoses. Masks can, as we’ve previously discussed, promote a sense of isolation and fear and some studies have shown the immunologic and psychologic hazards to children who are forced to wear masks for prolonged periods of time. At the outset of the pandemic, WHO experts advised that use of facemasks is not recommended as potential benefits are rather limited and there is a potential risk of self-contamination if used improperly. Another research study  shows that a moist mask is a breeding ground for (antibiotic resistant) bacteria and fungi, which can undermine mucosal viral immunity. 

Several studies show that long-term exposure to socio-psychological stress leaves neuro-epigenetic scars that are difficult to cure in young people and often escalate into mental behavioural problems and a weakened immune system  A recent study by the CDC concludes that in young adults (18-24 years), the level of anxiety and depression has increased by 63% (!) since the corona crisis. A quarter of them think about suicide.  As a result, the use of antidepressants has increased by 25%. 

It's critical to engage your children in conversations when not wearing facial coverings, to help activate neural regions that allow us to identify and store patterns, support facial recognition processes, and develop social cues comprehension.

It’s so important for parents and caregivers to be aware of any changes in a child’s behavior, or if they express new symptoms, and report these to your pediatrician or specialist. Ask for support with stress management techniques or ways to help your child cope, particularly if there are significant life events that occur or affect routines. 
 
As the situation in our lives continues to evolve and more changes may occur, please remember too to be kind to yourself, whether that means taking some time to go for a walk, to read a book or just relax with a few minutes of meditation. Self-care isn’t selfish, it’s really one of the best things you can do for your child, your family, and for YOU. As always, if you have questions or need to schedule a visit, please don’t hesitate to reach out – we are here to help! 

“There can be no keener revelation of a society’s soul,” Nelson Mandela famously said, “than the way in which it treats its children.”
 
In hope and healing,
Dr. Suzanne Gazda
 
For more reading…
 
Visit our Helpful Links section and be sure to check out some of our related articles in the blog library including:
 
https://www.suzannegazdamd.com/blog/pans-and-pandas-is-making-the-newsbut-what-do-we-really-know
 
https://www.suzannegazdamd.com/blog/our-childrens-mental-health-in-the-wake-of-a-pandemic
 
https://www.suzannegazdamd.com/blog/our-childrens-pandemic-of-neuro-immune-disorders
 
References:
 
1 Guido CA, Loffredo L, Zicari AM, Pavone P, Savasta S, Gagliano A, Brindisi G, Galardini G, Bertolini A and Spalice A (2021) The Impact of the COVID-19 Epidemic During the Lockdown on Children With the Pediatric Acute-Onset Neuropsychiatric Syndrome (PANDAS/PANS): The Importance of Environmental Factors on Clinical Conditions. Front. Neurol. 12:702356. doi: 10.3389/fneur.2021.702356