Inflammation

Perimenopause as a Hidden Trigger of Migraines

It is well-established that migraine attacks can be triggered by hormone changes. If you’re navigating perimenopause and notice an increase in headache intensity or frequency – you’re not alone. Some women find that migraines worsen during this life phase, while some experience migraines for the first time as their hormone levels shift. While many women with migraines are diagnosed in their teens or 20s, roughly 8 to 13% don’t get diagnosed until they are in perimenopause because their symptoms – including headaches, nausea, and fatigue – become much more intense[i]

 

Hormones and Migraines: The Connection

It is not clearly known why hormonal shifts can cause an increase in migraines. Some research suggests that changes in estrogen levels make certain cells more excitable – which may make you more sensitive to migraine triggers[ii]. Estrogen doesn’t just impact reproductive health; it plays a vital role in managing pain by controlling key brain neurotransmitters. When levels drop, the brain becomes more susceptible to pain signals, which can make migraines feel more intense and frequent. Fluctuating estrogen can also increase a person’s mast cells – a type of immune cell that triggers inflammation in the brain and often increases headache pain.

 

Why Estrogen Dominance Matters

Most research is on the effect of low estrogen in menopause (defined as not having a menstrual bleed for a year), but clinically I find that women in perimenopause can be affected even more frequently due to estrogen dominance.

Estrogen dominance happens when estrogen levels are high compared to progesterone. In perimenopause, a decrease in progesterone levels is the most common hormonal shift, usually happening in late 30s or early 40s. This can lead to symptoms like heavier menstrual bleeding, anxiety, and insomnia. But remember – the estrogen levels have not increased, but there is an imbalance.

Your liver also plays a role here. Women are often not metabolizing and eliminating their estrogen efficiently through their liver pathways, which can lead to additional challenges with weight gain, irritability, body pain, and of course, more frequent migraines.

 

Testing Your Hormone Levels

The symptoms of hormonal imbalance can be very clear, but there is a valuable and objective tool we recommend: the DUTCH Test. Unlike a standard blood test, this advanced 24-hour urine test measures estrogen and progesterone levels over a full day and evaluates how well your liver is metabolizing estrogen. With the DUTCH Test, we can get an in-depth look at your hormonal landscape, helping us create a tailored approach to bring your body back to balance.

 

 

Relief is Possible

The good news? Estrogen dominance and its symptoms can be addressed with strategic diet and lifestyle changes and targeted supplementation. Nutrients from cruciferous vegetables (broccoli, cauliflower, brussels sprouts, cabbage, etc.) can support liver health and help balance estrogen levels. Pairing these with dietary tweaks can make a big difference in reducing migraine frequency and severity.

Once you have identified your hormonal imbalance and have a plan, women usually experience improvements within a few weeks. Migraines can significantly affect your quality of life, but with the right support, relief is within reach.

 

Yours in good health,

Dr. Darlene Reid, ND


[i] Pavlović JM. The impact of midlife on migraine in women: summary of current views. Womens Midlife Health. 2020 Oct 6;6:11. doi: 10.1186/s40695-020-00059-8. PMID: 33042563; PMCID: PMC7542111.

[ii] Reddy N, Desai MN, Schoenbrunner A, Schneeberger S, Janis JE. The complex relationship between estrogen and migraines: a scoping review. Syst Rev. 2021 Mar 10;10(1):72. doi: 10.1186/s13643-021-01618-4. PMID: 33691790; PMCID: PMC7948327.

From Cloudy to Clear: Naturopathic Approaches to Combat Brain Fog

Have you noticed that your brain has been feeling like a haze lately? Maybe you’re having concentration difficulties or can’t recall familiar places or items as easily. Have you been repeating parts of a conversation over and over again?

You might be experiencing what is known as “brain fog” - a term often used to describe a state of mental cloudiness or cognitive dysfunction which can significantly impair one’s ability to function optimally in daily life. Brain fog is commonly associated with conditions like fibromyalgia, hormonal imbalances, and chronic fatigue syndrome, and underlying causes can vary widely from person to person. As naturopathic doctors, our approach involves diving deeper in the root causes of brain fog and utilizing various tools and tests to uncover underlying imbalances and provide individualized treatment strategies.

 

The tools that a naturopathic doctor may use to investigate can include the following:

Hormone testing – hormonal imbalances, such as thyroid dysfunction or adrenal fatigue can lead to impairments in cognitive function.

Metabolic assessments – blood sugar imbalances and insulin resistance has been shown to affect cognitive function, so your ND may want to test fasting blood glucose, fasting blood insulin, and HbA1c.

Nutrient deficiencies – screening for low iron, vitamin B12 or Vitamin D levels is recommended.

Markers of inflammation – hs-CRP and ESR may be tested within the bloodstream since inflammation has been shown to be triggered by various poor diet and lifestyle choices and external stressors and infections. 

Food sensitivity tests – food sensitivities which are IgG-mediated can lead to inflammation within the body and manifest as cognitive symptoms.

Environmental exposures – exposures to heavy metals, pesticides, mold and other toxins have been shown to impair cognitive function.

 

As naturopathic doctors, our focus lies in identifying and addressing the root causes of brain fog using a combination of conventional laboratory tests, functional assessments, and lifestyle modifications. By addressing these nutritional deficiencies, hormonal imbalances, metabolic dysregulation, inflammation, food sensitivities and environmental exposures, we can help patients regain mental clarity and improve their overall well-being.

In good health,

Dr. Sami Leung, ND

 

References

  1. Ettleson, M. D., Raine, A., Batistuzzo, A., Batista, S. P., McAninch, E., Teixeira, M. C. T., ... & Bianco, A. C. (2022). Brain fog in hypothyroidism: Understanding the patient’s perspective. Endocrine Practice28(3), 257-264.

  2. Fog, W. C. B. Causes of Brain Fog: Does Brain Fog Begin In Your Gut?

  3. Lucius, K. (2021). “Brain Fog”: Exploring a Symptom Commonly Encountered in Clinical Practice. Alternative and Complementary Therapies27(1), 23-30.

  4. Schmidt, S. (2019). Brain Fog: Does air pollution make us less productive?

  5. Wilson, L. (2008). Brain fog. The Center for Development. Retrieved on October 9, 2009.

  6. Yoshimura, H. (2023). Functional Medicine for Mental Clarity: Combating Brain Fog Naturally. Mental Health.

Does Sugar Impact Our Immune System?

We all know it’s not ideal to have a diet high in sugar. Most of us know this with respect to managing our weight – but what about the immune system? What about colds, flus, autoimmune conditions, diabetes, cancer – does sugar consumption make us more susceptible? And if it does, how much does it take to make a difference?  Before we dive in, lets do a quick review of the immune system.

Above you’ll notice two main subdivisions of our immune system. We have our innate immunity, which can be thought of as the offense players and the adaptive immunity which could be considered the defence players. The innate immune system is first to respond (within minutes to hours) when there is a foreign invader. It’s the part of our immune system responsible for mounting a fever and initiating inflammation. Inflammation is useful in the short term for acute injuries or illnesses. Long term however, inflammation plays a strong role in the development of several diseases such as autoimmune diseases, cardiovascular disease, diabetes mellitus, chronic kidney disease, non-alcoholic fatty liver disease and neurodegenerative disorders3. The innate immune response has no memory which means it responds the same way to all encountered pathogens. The adaptive immune system, also known as “acquired immunity” takes days to weeks to kick in. It is very specific and diverse to each type of pathogen it encounters which means it mounts a unique response to each pathogen after it has been “primed” or exposed to that pathogen. The adaptive immune system does have a memory which means it will respond faster the next time you are exposed to that pathogen.

 

How does sugar affect the immune system?

When we consume foods high in simple sugars, we get a post prandial (post meal) spike in the amount of sugar and triglycerides in our blood[1]. This is also known as “post prandial dysmetabolism” and it induces a wide variety of negative changes in the body. Just one high sugar meal can trigger transient effects such as:

Inhibition of neutrophils[2]

o  Neutrophils are part of the innate (first response) immune system. They patrol for foreign invaders and then trap and kill pathogens when discovered. High blood sugar prevents neutrophils from being able to get to the site of microbial infection (inhibition of migration), decreases their ability to trap pathogens (phagocytosis), and furthermore inhibits their ability to kill microbes2.

Increased inflammation and inflammatory markers such as C-reactive protein1

o  Long term inflammation (such as with repeated exposure to a diet high in sugar) can cause a breakdown of immune tolerance which may lead to major alterations in all tissues and organs, as well as normal cellular physiology, which can increase the risk for various non-communicable diseases in both young and older individuals[3]. It can also impair normal immune function leading to increased susceptibility to infections and tumors as well as poor response to vaccines3.

Immediate oxidant stress (free radical production)1

o  Oxidant stress acutely triggers inflammation which negatively impacts the immune system3. In addition, this oxidant stress also increases LDL oxidation, vessel constriction and clot formation, all of which contribute to cardiovascular disease1.

Endothelial (blood vessel) dysfunction1 2

o  High blood sugar decreases blood vessel dilation (reducing blood flow) while simultaneously increasing leakiness of the blood vessels and how quickly the blood clots due to the inflammatory response. This reaction is similar to how a viral infection would trigger vascular inflammation leading to endothelial dysfunction, coagulation and cardiovascular disease[4]. Long term vessel “hyperpermeability” has been associated with increased aging and diseases such as Parkinson’s and Alzheimer’s[5].

Glycosylation of proteins and alteration of tertiary structures of complement2

o  While this might sound complicated, what is important to understand is that these changes make it difficult for the body to recognize foreign pathogens and eliminate them2. Changes in glycosylation may increase the inflammatory response, enable viral immune evasion (ability to escape), and promote cancer cell metastasis[6]. Auto-immune disease development such as lupus and irritable bowel disease involve glycosylation of one or more glycoproteins6.

This diagram shows a summary of how systemic chronic inflammation (SCI) develops and what it can lead to. 

 

How much sugar does it take?

To provide a little bit of context, the chart below shows the immediate effects of consuming a beverage containing 75g of glucose. This amount of sugar is similar to a cup and a half of white rice (68g). You will notice that within a few hours the amount of glucose and triglycerides increase significantly which leads to immediate oxidant stress (nitrotyrosine), inflammation (C reactive protein [CRP]) and endothelial dysfunction via decreased blood flow via reduction in the diameter of blood vessels (FMD).

 

Another study looking at the immediate effects of sugar consumption found that people who consumed 40 grams of added sugar from just one 375ml can of soda experienced an increase in inflammatory markers, insulin resistance and LDL cholesterol[7].

 

In addition to the above, high sugar containing meals can alter our gut barrier function and drive gut bacteria imbalances (also known as dysbiosis). This can lead to what is referred to as “leaky gut” or intestinal permeability which fuels inflammation and taxes the immune system further[8]. In addition, altered gut bacteria has been suggested to contribute to a multitude of immune-mediated disorders such as irritable bowel disease [9]. Furthermore, as mentioned above, diets high in sugar have been implicated in the development of all kinds of diseases such as cardiovascular disease, type two diabetes, obesity, non alcoholic fatty liver disease, gout and autoimmune conditions such as rheumatoid arthritis[10].

 

How much sugar should we have and how can we reduce the negative impacts of sugar on our immune system and overall health?

The Heart and Stroke Foundation recommends that you consume no more than 10% of your total calories per day from added sugar – ideally less than 5%[11]. This means for someone with a 2000 calorie/day diet you should consume less than 48g (10%) of sugar. This is slightly more than one can of pop. The following are some key things you can consider doing to reduce the impact of high sugar foods on your immune system and overall health:

Fiber and low glycemic carbohydrates:

o  When eating carbohydrates, try to choose high fiber, low glycemic index (glycemic index <55) foods such as whole grains, beans and legumes, vegetables and berries. Carbohydrates in these forms are much harder to digest thus slowing the rate sugar enters the blood stream.

Protein and fat

o  Ensure you consume a healthy source of protein and/or fat with each meal or snack. The addition of protein and fat also helps to slow the rate sugar is released into the blood stream which prevents a spike in blood sugar. An example might be having almond butter with your banana.

o  Below on the left is an example of how adding whey protein to the same glucose drink reduced the increase of blood sugar after drinking1. On the right we have an example of how adding 90g of almonds to a high glycemic index meal reduced the area under the curve for glucose by 58%1.

Vinegar:

o  Research suggests that 1-2 tablespoons of vinegar added to a meal can lower post prandial glucose by 25%-35% as well as increase post meal satiety by more than two-fold1.

Avoid low glycemic and highly processed foods/beverages

o  Avoid highly processed foods and beverages which often contain high amounts of simple sugars, high fructose corn syrup and white flour.

Walk/Exercise

o  Walk for 10-30 minutes after each meal[12]. Short walks after each meal were found to be more effective for blood sugar control than one-time daily exercise regimes or the use of metformin alone[13] [14].

 

Reading food labels can help you make an informed decision on the foods you are eating. Remember, the daily recommended amount of sugar is less than 48g.

Ex: Tropicana – One serving of Tropicana juice is 34g of sugar. This is 72% of the recommended daily intake of sugar. In addition, orange juice in general is considered to have a glycemic index of 66-76 which is considered moderately to very high in regard to how much it will raise our blood sugar. 

 

Another example is BBQ sauce. Bulls Eye BBQ sauce has 12g of sugar/2tbsp. This means that just two tablespoons equal to 25% of the daily recommended sugar intake. However often in meals with BBQ sauce (such as a burger) we are having a bun, and ketchup and french-fries as well. This one meal quickly throws us far over the daily recommended intake.

 

Working with a healthcare provider can help you pinpoint which risk factors you have and how to safely reduce your risk and support better overall immune health. Be sure to talk with your health care provider before making any drastic lifestyle or dietary changes.

 

 

In health,

Dr. Brittany Pearce, RHN., ND.


[1] O'Keefe JH, Gheewala NM, O'Keefe JO. Dietary strategies for improving post-prandial glucose, lipids, inflammation, and cardiovascular health. J Am Coll Cardiol. 2008 Jan 22;51(3):249-55. doi: 10.1016/j.jacc.2007.10.016. PMID: 18206731.

[2] Jafar N, Edriss H, Nugent K. The Effect of Short-Term Hyperglycemia on the Innate Immune System. Am J Med Sci. 2016 Feb;351(2):201-11. doi: 10.1016/j.amjms.2015.11.011. PMID: 26897277.

[3] Furman, D., Campisi, J., Verdin, E. et al. Chronic inflammation in the etiology of disease across the life span. Nat Med 25, 1822–1832 (2019). https://doi.org/10.1038/s41591-019-0675-0

[4] Xu S, Jin T, Weng J. Endothelial Cells as a Key Cell Type for Innate Immunity: A Focused Review on RIG-I Signaling Pathway. Front Immunol. 2022 Jul 5;13:951614. doi: 10.3389/fimmu.2022.951614. PMID: 35865527; PMCID: PMC9294349.

[5] Oakley R, Tharakan B. Vascular hyperpermeability and aging. Aging Dis. 2014;5(2):114-125. Published 2014 Apr 1. doi:10.14336/AD.2014.0500114

[6] Reily C, Stewart TJ, Renfrow MB, Novak J. Glycosylation in health and disease. Nat Rev Nephrol. 2019 Jun;15(6):346-366. doi: 10.1038/s41581-019-0129-4. PMID: 30858582; PMCID: PMC6590709.

[7] Aeberli I, Gerber PA, Hochuli M, Kohler S, Haile SR, Gouni-Berthold I, Berthold HK, Spinas GA, Berneis K. Low to moderate sugar-sweetened beverage consumption impairs glucose and lipid metabolism and promotes inflammation in healthy young men: a randomized controlled trial. Am J Clin Nutr. 2011 Aug;94(2):479-85. doi: 10.3945/ajcn.111.013540. Epub 2011 Jun 15. PMID: 21677052.

[8] Camilleri M. Leaky gut: mechanisms, measurement and clinical implications in humans. Gut. 2019 Aug;68(8):1516-1526. doi: 10.1136/gutjnl-2019-318427. Epub 2019 May 10. PMID: 31076401; PMCID: PMC6790068.

[9] Zheng, D., Liwinski, T. & Elinav, E. Interaction between microbiota and immunity in health and disease. Cell Res 30, 492–506 (2020). https://doi.org/10.1038/s41422-020-0332-7

[10] Moling O, Gandini L. Sugar and the Mosaic of Autoimmunity. Am J Case Rep. 2019;20:1364-1368. Published 2019 Sep 15. doi:10.12659/AJCR.915703

[11] https://www.heartandstroke.ca/healthy-living/healthy-eating/reduce-sugar

[12] Bellini A, Nicolò A, Bazzucchi I, Sacchetti M. The Effects of Postprandial Walking on the Glucose Response after Meals with Different Characteristics. Nutrients. 2022;14(5):1080. Published 2022 Mar 4. doi:10.3390/nu14051080

[13] Pahra D, Sharma N, Ghai S, Hajela A, Bhansali S, Bhansali A. Impact of post-meal and one-time daily exercise in patient with type 2 diabetes mellitus: a randomized crossover study. Diabetol Metab Syndr. 2017;9:64. Published 2017 Aug 31. doi:10.1186/s13098-017-0263-8

[14] Erickson ML, Little JP, Gay JL, McCully KK, Jenkins NT. Postmeal exercise blunts postprandial glucose excursions in people on metformin monotherapy. J Appl Physiol (1985). 2017 Aug 1;123(2):444-450. doi: 10.1152/japplphysiol.00213.2017. Epub 2017 May 18. PMID: 28522762.

 

Omega-3s for Inflammation-Associated Depression

Essential Fatty Acids (EFAs)

Omega-3 and omega-6 fatty acids are essential fatty acids, meaning the body cannot make them on its own so they must be obtained through diet. They are both polyunsaturated fatty acids, however, they are found in different foods and have different roles in the body. Omega-3s are found in fish, nuts, seeds, and plant oils, while omega-6s are found in meats, vegetable oils, nuts, seeds, and processed foods.

dreamstime_s_72118275.jpg

The body requires a balance of omega-3 and omega-6 fatty acids for good health. However, the western diet is abundant in omega-6-rich foods, shifting this balance in some cases by 20:1 or higher. While both beneficial and necessary for the maintenance of good health, omega-3 and omega-6s have opposite effects on inflammatory modulation – the omega-6 pathway being more pro-inflammatory, the omega-3 being more anti-inflammatory.

Inflammation & Depression

Neuroinflammation is an inflammatory response within the brain and is a known component of many brain disorders. Rapaport et al., conducted a study exploring whether inflammatory biomarkers might act as measures of clinical response to omega-3 fatty acids – specifically eicosapentaenoic acid and docosahexaenoic acid – in subjects with Major Depressive Disorder (MDD).

The subjects were assessed for their baseline biomarkers of inflammation, as well as the presence and severity of their depressive symptoms using the Hamilton Depression rating scale. They were then randomized to 8 weeks of double-blind treatment with eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or placebo. Those given EPA who had high inflammation consistently reported a significant decrease of depressive symptoms by treatment week 8. While also critical to brain function, DHA did not produce the same effect. This difference is possibly explained by the fact that EPA has the ability to dampen the inflammatory response, while DHA does not.

This study highlights the importance of individualized assessment and treatment in mental health, and the value of EPA as part of a comprehensive treatment plan for depression.

Written by Dr. Jacalyn Sieben ND

References:

Kalkman H. O. (2020). The Association Between Vascular Inflammation and Depressive Disorder. Causality, Biomarkers and Targeted Treatment. Pharmaceuticals (Basel, Switzerland), 13(5), 92. https://doi.org/10.3390/ph13050092

Rapaport, M. H., Nierenberg, A. A., Schettler, P. J., Kinkead, B., Cardoos, A., Walker, R., & Mischoulon, D. (2016). Inflammation as a predictive biomarker for response to omega-3 fatty acids in major depressive disorder: a proof-of-concept study. Molecular psychiatry, 21(1), 71–79. https://doi.org/10.1038/mp.2015.22