Pearl Lee, PharmD, IFMCP

Root Causes of Anxiety & Depression

Anxiety and depression have become increasingly prevalent, affecting millions of individuals worldwide. As many factors can contribute to these conditions, it is essential to understand the root causes. This allows us to develop effective treatment strategies and when possible, avoid use of medications with potentially harmful side effects. Let’s delve into these potential root causes of anxiety and depression.


Blood Sugar Balance

Blood sugar levels play a vital role in mental well-being. Fluctuations in blood sugar levels can lead to mood swings, irritability, and anxiety. When we consume refined carbohydrates and sugary foods, blood sugar levels spike rapidly, followed by a rapid crash, leading to a cycle of highs and lows that can exacerbate anxiety and depression. Some people even experience panic attacks due to blood sugar crashes. To avoid these blood sugar fluctuations, eat balanced meals with plenty of fiber (vegetables), healthy fats and protein. For more specific guidance, check out – Guide to Healthy Eating.

Nutrient Deficiencies

There are several nutrient deficiencies known to be linked with anxiety and depression. These nutrient deficiencies may stem from poor intake, inadequate absorption, or increased use in the body. There may also be a genetic component when it comes to individual needs. Both dietary changes and supplementation may be utilized to replenish these nutrients.

Omega-3 fatty acids, specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been linked to mental health. Studies have shown that individuals who consume low amounts of fish or omega-3s are more likely to suffer from depression. Good dietary sources of omega-3 fatty acids include fatty fish (such as salmon, mackerel, and sardines), flaxseeds, chia seeds, and walnuts. However, supplementation is often needed to maintain adequate levels.

Vitamin D plays a crucial role in brain health, and deficiencies have been linked to mood disorders. As such, low vitamin D levels may be associated with an increased risk of depression and anxiety. Like omega-3s, supplementation is often needed for adequate levels. Natural sources of vitamin D include sunlight exposure (without sunscreen!), fatty fish, and egg yolks.

B vitamins are involved in brain function and the production of neurotransmitters. Deficiencies in vitamins B6, B12, and folate (B9) have been linked to an increased risk of depression and anxiety. Good dietary sources of B vitamins include whole grains, legumes, leafy greens, nuts, seeds, and animal products such as meat, fish, and dairy.

Magnesium is an essential mineral involved in numerous biochemical processes in the body, including those related to brain function. Low magnesium levels have been associated with increased anxiety and depression symptoms. Good dietary sources of magnesium include leafy greens, nuts, seeds, whole grains, and legumes.

Iron, when low, has been associated with fatigue, low mood, and poor cognitive function. As it is involved in many neurological activities, iron deficiency anemia has been shown specifically to cause anxiety and depression, with improvement after iron supplementation. Food sources richest in heme iron include lean meats and seafood, which are better absorbed. Nonheme iron sources include foods such as beans, lentils and spinach and are better absorbed when combined with vitamin C rich foods.

Zinc is an important mineral involved in brain function and the regulation of neurotransmitters. Inadequate zinc levels have been associated with symptoms of anxiety and depression. Food sources of zinc include oysters, red meat, poultry, beans, nuts, and seeds.

Hormones

Cortisone – stress hormone

Cortisol dysregulation from stress can be a contributing factor to the development of anxiety and depression. While stress itself is a normal and natural response to challenging or threatening situations, excessive or prolonged stress can overwhelm an individual’s ability to cope and adapt, leading to negative effects on mental health. 

Thyroid hormones

Thyroid hormones are involved in regulating neurotransmitters in the brain that are linked to mood, such as serotonin and norepinephrine. When there is an imbalance in thyroid hormone levels, it can disrupt the normal functioning of these neurotransmitters, potentially leading to mood disturbances, including anxiety and depression. For example, hypothyroidism is a cause of depression and hyperthyroidism (less common) may cause symptoms of anxiety.

Estrogen & Progesterone

Fluctuations in estrogen levels, whether too high or too low, can contribute to mood swings, anxiety, and depression. This is especially prevalent for women during perimenopause or postpartum. However, it can occur at any time when hormones are out of balance. For example, estrogen dominance can cause PMS and associated mood symptoms. When there is estrogen dominance, there is low progesterone relative to estrogen and increased likelihood of anxiety. We need sufficient progesterone for its calming effect. Though it’s known as the “female” hormone, estrogen excess can affect men as well, and is often coupled with decreased testosterone. 

Testosterone

Adequate levels of testosterone are generally associated with an improved sense of well-being and positive mood. Studies have suggested that higher levels of testosterone may contribute to feelings of confidence, motivation, and overall happiness. Consequently, low testosterone levels are linked to anxiety and depression.

Gut Health

The gut-brain axis is a complex bidirectional communication system connecting the gastrointestinal tract and the central nervous system. Disruptions in gut health, such as dysbiosis (imbalanced gut bacteria) and increased intestinal permeability, commonly known as “leaky gut,” have been linked to mental health disorders. This increased permeability allows substances such as toxins, bacteria (especially lipopolysaccharides – LPS from “bad bacteria”), and undigested food particles to leak from the intestines into the bloodstream. When these substances enter the bloodstream, they can trigger an immune response, leading to inflammation in the body. Systemic inflammation has been shown to be connected to anxiety and depression, potentially through cytokine production and subsequent neuroinflammation.

In Summary…

Anxiety and depression are complex conditions influenced by various interconnected factors. Understanding the potential root causes, such as blood sugar balance, nutrient deficiencies, hormone imbalance, and gut dysbiosis, allows for a comprehensive approach to treatment. While these may be common root causes, it is not all of them. For example, trauma has a very real effect on anxiety and depression, and individuals may benefit from specialized treatment such as EMDR.  Specific lifestyle factors must be taken into consideration, such as exercise, which has been shown to improve anxiety and depression and poor sleep which can contribute to increased anxiety and depression. An individual’s symptoms may be multifactorial, stemming from more than one root cause. Using a functional medicine approach and addressing these underlying factors through personalized interventions, including dietary modifications, targeted supplementation, stress management techniques, and hormone balancing, mental well-being can be restored with improvements in overall quality of life. 

 


 

References:

Daneshzad, E., Keshavarz, S.-A., Qorbani, M., Larijani, B. and Azadbakht, L. (2020), Association between a low-carbohydrate diet and sleep status, depression, anxiety, and stress score. J Sci Food Agric, 100: 2946-2952. https://doi.org/10.1002/jsfa.10322

Melanson KJ. Nutrition Review: Relationships of Nutrition With Depression and Anxiety. American Journal of Lifestyle Medicine. 2007;1(3):171-174. https://doi:10.1177/1559827607299725

Lee, HS., Chao, HH., Huang, WT. et al. Psychiatric disorders risk in patients with iron deficiency anemia and association with iron supplementation medications: a nationwide database analysis. BMC Psychiatry 20, 216 (2020). https://doi.org/10.1186/s12888-020-02621-0

Gençay Can, A., Can, S. S., Atagun, M. İ. & Akçaer, E. T. (2018). Is Iron Deficiency Anemia Associated with Cognitive Functions in Reproductive-Age Women? . Ankara Medical Journal , 18 (4) , 470-478 . https://doi.org/10.17098/amj.499650

Kumar, R., LeMahieu, A. M., Stan, M. N., Seshadri, A., Ozerdem, A., Pazdernik, V. K., Haynes, T. L., Daugherty, D. H., 3rd, Sundaresh, V., Veldic, M., Croarkin, P. E., Frye, M. A., & Singh, B. (2023). The Association Between Thyroid Stimulating Hormone and Depression: A Historical Cohort Study. Mayo Clinic proceedings, 98(7), 1009–1020. https://doi.org/10.1016/j.mayocp.2022.12.020

Kundakovic, M., & Rocks, D. (2022). Sex hormone fluctuation and increased female risk for depression and anxiety disorders: From clinical evidence to molecular mechanisms. Frontiers in neuroendocrinology, 66, 101010. https://doi.org/10.1016/j.yfrne.2022.101010

Limbana, T., Khan, F., & Eskander, N. (2020). Gut Microbiome and Depression: How Microbes Affect the Way We Think. Cureus, 12(8), e9966. https://doi.org/10.7759/cureus.9966

 

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