Vitamin D and Your Immune System


The nutrient I wanted to summarize is Vitamin D. I have been fascinated with the role of vitamin D in health topics such as autoimmunity for my own personal reasons. I feel that raising my levels of Vitamin D has been key in my immune system and healing from my autoimmune disease. There is increasing epidemiologic evidence linking vitamin D deficiency and autoimmune diseases including multiple sclerosis (MS), rheumatoid arthritis (RA), diabetes mellitus (DM), inflammatory bowel disease and systemic lupus erythematosus (SLE) (Aranow, 2011).

Vitamin D is sometimes called a pro-survival molecule, having anti-inflammatory and immunomodulating action, giving it “stress-quenching activity” (Chirumbolo, Bjorklund, Sboarina, & Vella, 2017).  In fact, research is demonstrating that vitamin D may have the abilities beyond its immune/anti-inflammatory role by inhibiting metabolic stress and energetic expenditure in a cell microenvironment (Chirumbolo et al., 2017). Vitamin D is considered to have a pleiotropic role in the immune system. According to Chirumbolo e al, Vitamin D is involved in the innermost balance of energetics and survival by the cell in its involvement in intracellular organelles of the cell such as the endoplasmic reticulum (ER).  An interesting suggestion comes from evidence of Vitamin D’s involvement in macrophage differentiation and foam cells” (Chirumbolo et al., 2017).

Vitamin D is growing a reputation to enhance human health in at least 4 processes.  Innate immunity, acquired and regulatory Immunity, inflammation, and gut integrity. The area I wanted to dig deeper into was the role of Vitamin D in innate immunity.

Innate Immunity

Researchers are finding that T cells rely on Vitamin D to become activated to detect and kill pathogens.  According to Professor Geisler from the Department of International Health, when a T cell is exposed to a foreign pathogen, it extends the Vitamin D receptor as a signaling device to search for Vitamin D.  “This means that the T cell must have vitamin D or activation of the cell will cease. If the T cells cannot find enough vitamin D in the blood, they won’t even begin to mobilize” (Science Daily, 2010).  T cells that are successfully activated can transform either into killer cells or helper T cells, but they need Vitamin D to perform this successfully.
The activity of vitamin D involves the gut-brain axis, and may play a role in the “hygiene hypothesis” (Chirumbolo et al., 2017).  As a modulatory hormonal molecule, vitamin D can inhibit an inflammatory response and activate regulatory immune mechanisms.  However, it is also “able to induce the production of antibacterial peptides from mononuclear cells and help innate cells to counteract bacterial infection” (Chirumbolo et al., 2017).   In a general way, some scientists consider Vitamin D as an interleukin rather than a “pleiotropic exogenous vitamin”, due to its ability to participate in innate immunity and inflammation, similar to a cytokine.  “Fundamentally, vitamin D dampens the LPS-induced inflammation in mononuclear immune cells (monocytes, macrophages, and DCs) acting on nuclear factor–κB (NF-κB) or p38MAPK via the VDR, which is fundamental to inhibit inflammation” (Chirumbolo et al., 2017).

It was interesting to find that Vitamin D has been previously used to treat infections such as tuberculosis before the era of effective antibiotics, using cod liver oil. In fact, there have been multiple cross sectional studies that associate lower levels of Vitamin D with increased infections.  This is thought to do be due the effects Vitamin D has on the innate immune system.  Vitamin D plays an important role in innate antimicrobial response.  It is thought that when macrophages recognize LPS through TLR, this can increase expression of the vitamin D receptor, and subsequent transcription of antimicrobial peptides (AMP’s) such as cathelicidin and beta defensin (Aranow, 2011).   These peptides show a broad spectrum of antimicrobial activity against bacterial, enveloped viruses and fungi (Kosciuczuk et al., 2012).  AMP’s are super important, since they involve the disintegration of cell membranes of organisms toward which the peptide is active, but do not act on healthy hose cell membranes (Kosciuczuk et al., 2012). Some actions of AMPS’s such as cathelicidins are mediated though their interaction with other cells which are the important part of innate immune system, like monocytes, dendritic cells, T cells and epithelial cells (Kosciuczuk et al., 2012) The susceptibility to bacterial infections of animals and humans with lowered expression of antimicrobial peptides shows their crucial role in the immune response.

Other effects vitamin D has on the immune system is involved in B and T cell mechanisms.  Vitamin D can inhibit B cell proliferation while blocking B cell differentiation and immunoglobulin secretion.  It can also suppress T cell proliferation resulting in subsequent shift from TH1 to TH2 phenotype.  It can also affect T cell maturation with a shifting away from TH17 expression, while facilitating the induction of T regulatory cells.  “These effects result in decreased production of inflammatory cytokines (IL-17, IL-21) with increased production of anti-inflammatory cytokines such as IL-10” (Aranow, 2011).  It can also inhibit monocyte production of inflammatory cytokines such as IL-1, IL-6, IL-8, IL-12 and TNF-a. It additionally inhibits DC differentiation and maturation, as evidenced by a decreased expression of MHC class II molecules, costimulatory molecules and IL-12.  Inhibition of DC differentiation and maturation is particularly important in the context of autoimmunity.

I believe we are just starting to uncover the effects the Vitamin D on the immune system, and it is something I am very interested in learning more deeply.  Some areas to look further include VDR mutations, why some people experience side effects from Vitamin D supplementation, enhancing vitamin D bioavailability from food and gut microbes.  “Given the importance of vitamin D for a functional immune system and the profound deficiency observed in autoimmune disease, as well as the correlation of deficiency with more active disease, an important issue is whether or not the immune components in autoimmune disease are capable of responding appropriately to vitamin D” (Aranow, 2011)


Aranow, C. (2011). Vitamin D and the immune system. J Investig Med, 59(6), 881-886. doi:10.2310/JIM.0b013e31821b8755

Chirumbolo, S., Bjorklund, G., Sboarina, A., & Vella, A. (2017). The Role of Vitamin D in the Immune System as a Pro-survival Molecule. Clin Ther, 39(5), 894-916. doi:10.1016/j.clinthera.2017.03.021

Kosciuczuk, E. M., Lisowski, P., Jarczak, J., Strzalkowska, N., Jozwik, A., Horbanczuk, J., . . . Bagnicka, E. (2012). Cathelicidins: family of antimicrobial peptides. A review. Mol Biol Rep, 39(12), 10957-10970. doi:10.1007/s11033-012-1997-x

Science Daily. (2010). Vitamin D crucial to activating immune defenses. Retrieved (2018, June 3) from


Attachment Parenting and Long Term Stress Response


I often wondered what impact childhood stress had on a developing child’s brain, particularly during infancy.  When my children were infants, I practiced co-sleeping, baby wearing, and attachment parenting. This created quite a bit of conflict with my ex-husband, who believed in sleep training.  I am glad we are discussing this topic, as it seems that sleep training can be viewed as a type of ACE.

The ‘cry it out’ approach seems to have arisen as a solution to the dissolution of extended family life in the 20th century (Narvaez, 2011).  The idea was, “a baby older than six months “should be taught to sit silently in the crib; otherwise, he might need to be constantly watched and entertained by the mother, a serious waste of time.” According to Narvaez (2011), “we know now that leaving babies to cry is a good way to make a less intelligent, less healthy but more anxious, uncooperative and alienated persons who can pass the same or worse traits on to the next generation”.

I recall during my Masters we studied the experiments on rats, called “Lick your Rats”.  This study was eye opening, as it showed the effects of rats that are nurtured vs. those who were not nurtured.  The researchers indicate that there are hundreds of genes affected by nurturance. In studies of rats with high or low nurturing mothers, there is a critical period for turning on genes and anxiety. “If in the first 10 days of life you have a low nurturing rat mother (the equivalent of the first 6 months of life in a human), the gene never gets turned on and the rat is anxious towards new situations for the rest of its life, unless drugs are administered to alleviate the anxiety (Naravez, 2011)”.  When a baby gets distressed during sleep training, high levels are cortisol are secreted.  It is thought that extreme stress and bouts of high cortisol can negatively influence neural development (Cassels, n.d.).  In cases of severe neglect, effects are seeing the development of white matter in the brain, hippocampus and amygdala. The child can develop a “stress-reactive profile”, similar to the rats in the study, in which they have a heightened response to stress.  Evolutionarily, this makes sense.  An infant raised in an environment in which he or she is not safe has to be acutely aware of the stress around them (Cassels, n.d).

I found it interesting that although babies are typically more hyporesponsive to cortisol and stress, the responsiveness depends on the source of stress.  In fact, separation from the caregiver happens to be one behavior that does elicit a cortisol response, especially if there is no other nurturing caregiver buffering the stress, such as another family member or babysitter.  Essentially, this means that if the baby is left with a non-nurturing caretaker, the negative effects of the separation stress are more impactful.  The behavior or circumstances that elicit cortisol spikes in infancy are moderate-severe pain, abuse, neglect, or abandonment of a caregiver with no responsive substitute.  Sleep training falls well into this category.

Moreover, the infants and their mothers had lost what is called “synchrony”.This is the physiological link between mother and infant, the link that allows mothers to help soothe their babies when upset, the link that is associated with attachment status.

I am happy to say I continued to stand for what I believed in and I coslept with both my children. My daughter was a bit more needy, as I saw immediately in the early days we tried to sleep train.  My motherly instinct took over immediately, and I coslept with her until she was 3 years old.  To this day, she loves when I sleep next to her (at age 10).  My son was a bit more independent, but he coslept for about 2 years.  When I first separated from my ex-husband, we shared a family bed for about a year.  I do not regret a moment of my decision.

“The functional effect of sensitive, responsive, attentive caregiving is that it allows children to express and experience distress, communicate those emotions to caregivers in ways that can elicit help, without stimulating increases in glucocorticoids” (Narvaez, 2011).



Cassels, T. (n.d.). “It’s Just a Little Cortisol”: Why Rises in Cortisol Matter to Infant Development. Retrieved (2018, May 29) from (Links to an external site.)

Narvaez, D. (2011, December 11).  “Dangers of Crying It Out”.  . Retrieved (2018, May 29) from

Adverse Childhood Events-and YOUR HEALTH


This week in Immunology, we are discussing Adverse Childhood Events and the influence it has on the immune system.  This module struck me deeply, as is inspired me to look more deeply at my own health history through the eyes of the functional medicine timeline.  Having an autoimmune disease, I often wondered what the connection with my childhood was with the inflammation that has contributed to my disease.  This information in this module was indeed eye opening.

Numerous studies have demonstrated that childhood adversities have the potential to increase the risk of many diseases that can increase the likelihood of premature mortality, due to increased levels of inflammation (Chen & Lacey, 2018).  As we know, chronic inflammation is associated with increased risk of diseases such as autoimmune disease, cancer, and diabetes (Chen & Lacey, 2018). Having an autoimmune disease myself, I am always looking to dig deeper at my own root causes.  I am not surprised that my childhood experiences could be playing a significant role.  Being born in a first generation Middle Eastern family, there was much pressure put on me as a child in regards to cultural differences that affected me in many ways.  Being repeatedly exposed to adverse childhood experiences (ACE) can affect the human stress regulatory system, which is accompanied by an increase in chronic inflammation.  I recall as early as in my teens having trouble with managing stress.  After I gave birth to my children, I felt as though my adrenals had “crashed” and was diagnosed with adrenal dysfunction at age 31.  Chronic exposures to stress is associated with a dysregulation of the HPA axis and sympathetic adrenocortical axis, which are accompanied by increased inflammation. The chronic inflammation that results is associated with some of the underlying mechanisms of various illnesses, through activation of the immune system. In other worse, dysregulation of the HPA axis, induced by chronic inflammation, put me in a state of immune dysfunction. In FDN, this is called “Metabolic Chaos”.  “The HPA axis is a powerful modulator of inflammatory activity and is in turn modulated by inflammatory processes, as well as being highly responsive to environmental adversities both in childhood and in adulthood” (Baumeister, Akhtar, Ciufolini, Pariante, & Mondelli, 2016).

Several previous studies have reported an association between childhood trauma and increased levels of pro-inflammatory markers, such as the acute phase protein C-reactive protein (CRP), and of the cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). This provides strong evidence that childhood traumatic events significantly impact on the inflammatory immune system, extending their influence into adult health (Baumeister et al., 2016).  It was particularly interesting to note that childhood trauma can even lead to greater methylation of the glucocorticoid receptor (GR), which is correlated with reduced GR function as demonstrated by a negative feedback loop of the HPA axis (Baumeister et al., 2016).  In addition, the increased inflammation can also impair GR function, leading to sustained GR resistance into adulthood.  Moreover, the GR is crucial in regulating TNF-α signaling and TNF-induced cytokine production, as well as conveying protection against TNF-related tissue damage (Baumeister et al., 2016).  It is apparent that dysregulation of the GR has far reaching impacts in regards to modulating inflammation.

Adverse childhood events can also contribute to metabolic syndrome.  Depression is one of the drivers that can contribute to physiological changes associated with metabolic syndrome.  In particular, depression can upregulate inflammatory processes that contribute to atherosclerosis, insulin resistance, and neurodegeneration (Danese et al., 2009).  Depression has been linked to multiple biological abnormalities, including vascular pathologic changes, autonomic function changes, HPA axis dysfunction, and in particular, immune dysfunction. Depression is associated with increased numbers of circulating leukocytes and pro inflammatory cytokines such as interleukin-1 (IL-1), interleukin-2 (IL-2) and interleukin-6 (IL-6). A hypothesis is that there is a positive feedback mechanism between depression and cardiovascular disease, as evidenced by increased levels of CRP in adulthood (which is often used to predict the development of cardiovascular disease).  This is compounded by metabolic abnormalities such as obesity, dyslipidemia, glucose intolerance, and hypertension that exert bi-directional influences on hormone function that lead to hormone imbalances (Danese et al., 2009).  “Many studies reported that the clinical depression can nearly double the risk of mortality and nonfatal cardiac events and that even subclinical elevations in depressive symptoms are related to a poorer prognosis in patients with established CVD” (Liu et al., 2017).

The progression is indeed bi-directional. Increased concentrations of pro inflammatory cytokines influence atherosclerotic plaque progression, poor lifestyle habits and sickness behavior. Poor lifestyle behaviors and sickness behavior can lead to an inactive depressed lifestyle that further heighten the risk of cardiovascular disease (Liu et al., 2017).

In regards to our role as clinical nutritionists, I think this is a great opportunity to education parents on the promotion of healthy psycho-social experiences for children as a potentially cost-effective strategy for the prevention of age-related disease.


Baumeister, D., Akhtar, R., Ciufolini, S., Pariante, C. M., & Mondelli, V. (2016). Childhood trauma and adulthood inflammation: a meta-analysis of peripheral C-reactive protein, interleukin-6 and tumour necrosis factor-alpha. Mol Psychiatry, 21(5), 642-649. doi:10.1038/mp.2015.67

Chen, M., & Lacey, R. E. (2018). Adverse childhood experiences and adult inflammation: Findings from the 1958 British birth cohort. Brain Behav Immun, 69, 582-590. doi:10.1016/j.bbi.2018.02.007

Danese, A., Moffitt, T. E., Harrington, H., Milne, B. J., Polanczyk, G., Pariante, C. M., . . . Caspi, A. (2009). Adverse childhood experiences and adult risk factors for age-related disease: depression, inflammation, and clustering of metabolic risk markers. Arch Pediatr Adolesc Med, 163(12), 1135-1143. doi:10.1001/archpediatrics.2009.214

Liu, R. H., Pan, J. Q., Tang, X. E., Li, B., Liu, S. F., & Ma, W. L. (2017). The role of immune abnormality in depression and cardiovascular disease. J Geriatr Cardiol, 14(11), 703-710. doi:10.11909/j.issn.1671-5411.2017.11.006

Allergies and Your Environment


Allergies are rampant!  I think everyone I know has one type of allergy, whether it skin related, upper respiratory or food!  What is going on?  Why is the prevalence of allergies exploding?  If you want to know more, read below….

Although the term allergy is used loosely to refer to any reaction as an allergy, the medical community defines an allergy as a precise cascade of biochemical reactions. In genetically predisposed (or atopic) individuals, these reactions result in very specific symptoms. Atopy refers to the tendency for asthma, eczema and hay fever, characterized by an overactive immune response to environmental factors (Stanway, 2004).  Symptoms include sneezing, wheezing, bronchoconstriction and even anaphylaxis (Rakel, 2018).

Much research has been focused upon the modification of the allergic immune response early in life, either during the prenatal period or early childhood. Atopy may be genetic, although environmental factors are thought to play a strong role in the development of atopy. Some examples include prenatal and postnatal infection exposure, timing of food introduction, and household pet exposure as predictors of atopy later in life (Rakel, 2018).  The antecedents I would like to focus on are related to environmental factors.

Environmental Factors

Environmental factors interact with genetic factors to maintain allergic (TH2) immune responses, which activate eosinophils, promote IgE production which drive up allergy symptoms (Delves, n.d.).  Interestingly, early childhood exposure to bacterial and viral infections and endotoxins may shift the immune response that can discourage allergic responses (Delves, n.d.).  Trends in developed countries toward smaller families with fewer children and cleaner indoor environments are often thought to contribute to a phenomenon known as the “hygiene hypothesis”. This hypothesis proposes that excess ‘cleanliness’ in an infant’s or child’s environment can lead to a decline in the number of infectious stimuli that are necessary for the proper development of the immune system (Stanway, 2004).  This includes early use of antibiotics that may limit children’s exposure to the infections that drive the opposite immune responses that drive down the allergic reponse, which can explain some of the rise of atopic allergies.  Other factors can include chronic allergen exposure, diet and environmental pollutants.

The hygiene hypothesis also indicates that the early microbial environment is also essential for proper development of protective antimicrobial and regulator immune responses to environmental antigens (Liu, 2015). For example, parents who orally “cleaned” their pacifiers were less likely to have allergic sensitization, eczema and asthma by 18 months (Liu, 2015).  Globally children who have older siblings demonstrate less risks of hay fever and eczema, which were more strongly correlated in more affluent countries (Liu, 2015).  Interestingly, having older siblings may also influence the microbiome.  “The infant gut microbiome associated with having older siblings was recently shown in a birth cohort to have more Bifidobacterium, Lactobacillus, Escherichia, and Bacteroidetes genera and less Clostridia” (Liu, 2015).

In another example, a house dust microbiome that is rich and diverse in the first year of life was negatively associated with allergic sensitization and atopic recurrent wheezing at age 3 years, possibly due to the abundance of Firmicutes and Bacteroidetes phyla.  The same trend has been demonstrated in a household that has dogs.

In laboratory models, oral exposure to extracts of house dust from homes with dogs prevented the development of allergy associated asthma while altering the gut microbiome, including enrichment of Lactobacillus johnsonii (Liu, 2015).

Another area that has been given attention lately is the relationship between allergic diseases and helminth infections. Yes, its a type of worm!  It has been demonstrated that helminths can induce a strong immune response while consequently being inversely associated with allergy and asthma!  These include inducing dentritic cells to induce IL-10 producing Treg lymphocytes while inhibiting allergic airways inflammation in laboratory models of asthma (Liu, 2015).  On the flip side, the innate immune system can also affect immune response against helminth infections which can induce inflammation. “This reaction is the body’s response to destroy helminths, especially tissue helminths that stimulate an excessive immune response that can promote allergies. Though inconclusive, it does demonstrate the role the microbial environment has on atopic allergic responses.



Delves, P. (n.d.) Overview of Allergic and Atopic Disorders. Retrieved (2018, May 22) from,-autoimmune,-and-other-hypersensitivity-disorders/overview-of-allergic-and-atopic-disorders

Liu, A. (2015). Revisting the hygiene hypothesis for allergy and asthma. J Allergy Clin Immunol 2015;136:860-5.

Rakel, D. (2018). Integrative Mecidine (Vol. 4): Elsevier Inc.


Sitcharungsi, R., & Sirivichayakul, C. (2013). Allergic diseases and helminth infections. Pathog Glob Health, 107(3), 110-115. doi:10.1179/2047773213y.0000000080

Stanway, A.  (2004). Causes of atopic dermatitis. Retrieved (2018, May 22) from


Mast Cell Activation and Inflammation


I love strawberries!  They are high in Vitamin C and just delicious on salads.  Sadly, they also can cause pain in many people who have mast cell activation disorder. Read below….

I have recently become very interested in histamine intolerance and mast cells, and strawberries is on the list of foods high in histamine. There is some significant research being done on mast cell activation, autoimmune disease and the immune system.  Histamine intolerance is the disequilibrium between accumulated histamine and histamine degradation (Manzotti, Breda, Di Gioacchino, & Burastero, 2016).  Histamine degradation is dependent on the primary enzyme, diamine oxidase (DAO). Histamine is a biogenic amine found in foods such as pickles, matured cheese, fermented foods and leftovers.  Some foods are histamine liberators and that includes fruits such as pineapples, bananas, citrus fruits, papayas and strawberries.  The ingestion of histamine rich foods can provoke a variety of symptoms such as digestive, arrhythmia, flushing, asthma, hypotension, rhinoconjunctivitis, and headaches.  Impaired DAO production is often the culprit, which can result in increased enteral histamine uptake and increased plasma histamine concentrations (Manzotti et al., 2016).  Interesting the study by Manzotti demonstrated that 71% of patients reported functional bloating after consuming high histamine foods.

The latest research indicates that mast cells that release histamine and other inflammation in the bloodstream are active participants in autoimmune disease related tissue damage.  Increased mast cell activity, release of histamine and other inflammatory agents are frequently seen in autoimmune conditions such as MS, RA and many others (Healing Histamine, n.d.).   A variety of receptors including those engaged by antibody, complement, pathogens, and intrinsic danger signals are implicated in mast cell activation in disease.  A variety of receptors including those engaged by antibody, complement, pathogens, and intrinsic danger signals are implicated in mast cell activation in disease (Brown & Hatfield, 2012).  Mast cells can also recruit other immune cells such as neutrophils, to the sites of autoimmune destruction.  “Mast cells can only act as accessory cells to the self-reactive T and/or antibody driven autoimmune responses” (Brown & Hatfield, 2012).  This includes mast cells among one of the major contributors to autoimmunity and should definitely be considered.

Autoimmune and allergic diseases share fundamentally important features in that both are the result of “hypersensitive” immune responses directed toward inherently harmless antigens (Brown & Hatfield, 2012).  An early progress of autoimmune disease involves the activation and expansion of T and/or antibody producing B cells that wear autoreactive receptors.  These autoreactive T or B cells can then enter the bloodstream and migrate to sites of inflamed tissues expressing relevant autoantigens (Brown & Hatfield, 2012). “T cells, through the elaboration of cytotoxic mediators, and antibodies, through complement fixation or their ability to activate resident accessory cells such as macrophages and mast cells via Fc receptor engagement, can play direct roles in tissue destruction at these sites” (Brown & Hatfield, 2012)

In addition to eliciting the above described adaptive immune response, antigens can engage a class of danger- associated receptors on both adaptive and innate immune cells, including mast cells.  These receptors include toll-like receptors (TLRs) and Nacht-LRRs (NLRs) (Brown & Hatfield, 2012).  Activation of immune cells through TLRs and NLRs induces the expression of multiple inflammatory mediators that can ultimately result in local tissue damage causing the release of normally sequestered tissue antigen (Brown & Hatfield, 2012). Subsequent recognition of these antigens by T or B cells will induce activation and initiate autoimmunity. Alternatively, infection-induced activation of accessory immune cells, including mast cells, macrophages, and neutrophils, can boost inflammation and transform a relatively modest autoreactive response.

There is evidence that other TLRs are expressed on mast cells.   For example, activation of mature mast cells through TLR2 results in their production of several pro-inflammatory cytokines critical in autoimmunity including IL-17, IFNγ, TNF, and IL-1β.  Mast cells also express multiple IgG Fc receptors. This is significant because IgG autoantibodies are hallmarks of many autoimmune diseases and have been detected in multiple autoimmune diseases.



Brown, M. A., & Hatfield, J. K. (2012). Mast Cells are Important Modifiers of Autoimmune Disease: With so Much Evidence, Why is There Still Controversy? Front Immunol, 3, 147. doi:10.3389/fimmu.2012.00147


Healing Histamine (n.d.).  Histamine Intolerance, Mast Cells & Autoimmunity.  Retrieved (2018, May 15) from


Manzotti, G., Breda, D., Di Gioacchino, M., & Burastero, S. E. (2016). Serum diamine oxidase activity in patients with histamine intolerance. Int J Immunopathol Pharmacol, 29(1), 105-111. doi:10.1177/0394632015617170

Erectile Dysfunction and Inflammation


Cytokines, are small secreted proteins released by cells have a specific effect on the interactions and communications between cells. Different cytokines are associated with different diseases or conditions(Zhang & An, 2007). One particular cytokine, TNF-α, has been shown to play an important role in ED as well as cardiovascular disease (CVD), due to the effect it has on the vascular system.  Patients with ED often show high levels of TNF-a, which is a cytokine that is often secreted by white blood cells in response to inflammatory stimuli.  In addition, the presence of a low-grade inflammatory process is associated with many cardiovascular diseases (CVD). Cytokines levels, such as TNF-α, are increased in response to inflammation and contribute to the changes in vascular reactivity observed in CVD (Carneiro et al., 2010). Two distinct surface receptors mediate the effects of TNF-α. These include TNFR-1, and TNFR-2.  Gene expression of TNFR-1 has been demonstrated in cavernosal tissue of the penis (Carneiro et al., 2010).  It has been pretty well established that this cytokine is an important contributor of many cardiovascular diseases related to endothelial dysfunction. Additionally, endothelial function is impaired in inflammatory conditions and conditions with increased oxidative stress.  In vivo laboratory administration of TNF-α demonstrates impairment of endothelium-dependent vasorelaxation in a variety of vascular beds and decreases the release of nitric oxide (NO), which is required for erectile function. TNF-α has the ability to increase arterial reactive oxygen species generation, which likely accounts for some of the reduction in NO levels.

So the question is, what is causing the TNF-α to be elevated?  I found the link to environmental toxins to be quite intriguing.  Could exposure to these toxins induce elevations in inflammatory cytokines, like TNF-α, that leads to downstream effects such as vascular dysfunction?  Some environmental toxins, such as endocrine disrupting chemicals (EDCs) interfere with the synthesis of cytokines, immunoglobulins, and inflammatory mediators, and they also affect the activation and survival of immune cells (Yang et al., 2014).  The dysfunction of the immune system caused by some EDCs may lead to immunity immunodeficiency against infection, or to hyperreactivity of immune responses, as seen in allergy and autoimmune disease (Yang et al., 2014).  Nonylphenol (NP), one of the alkylphenols, is the most important metabolite of a group of nonionic surfactants, is a common EDC that can bioaccumulate through the diet.  It is structurally similar to estrogen, which can feminize male animals and may be linked to infertility.  Some in vitro or ex vivo studies suggest that NP skews T cells towards Th2 responses through its influence on dendritic cells (DCs), resulting in increased expression of IL-6 and TNF-α, but not IL-10 and IL-12, in response to LPS stimulationNP increases the expression of TNF-α, but suppressed anti-inflammatory cytokine IL-10 production in a range of physiological doses, burning both ends of the candle.

Another interesting association with increased levels of TNF-α is associated with intestinal parasites such as Entamoeba histolytica.  Although TNF can be synthesized and secreted by many other cell types, such as neutrophils, eosinophils, and mast cells, the main source of TNF is activated macrophages.  Usually, TNF contributes to the control of parasitic and bacterial infection like in the case of Trypanosoma infection or by triggering an immune response. E. histolytica activates the inflammatory process by promoting TNF production, which is thought to be crucial for guiding E. histolytica towards TNF-producing cells of the host. One may speculate that this behavior is triggered by its need of nutrients that cannot be satisfied in the inflamed tissues. Inflammation causes change in the gastrointestinal microbiota, and these changes may provoke E. histolytica to search for alternative sources of nutrients.

Other intestinal parasites have been associated with HPA axis dysfunction, since the immune and neuroendocrine systems are interconnected by a network in which hormones, antigens, receptors, cytokines, antibodies and neuropeptides modulate immune response. This indicates that intestinal parasites can influence sex hormone production, such as testosterone.  Low testosterone levels often go hand in hand with erectile dysfunction, but that will be discussed in a future blog.

The bottom line; get to the bottom of the problem. Find the source of the inflammation that is ruining your sex life. Run functional labs such as a stool test to rule out intestinal parasites.  An HPA axis test, such as the Dutch Complete, can determine the hormone imbalance and potentially identify the root cause. An environmental toxin test can reveal if toxins are ruining contributing to your immune dysfunction.  Running these labs will allow you to get on a healing path so you can get off the purple pill and regain your life back. You should work with a practitioner who is knowledgeable about the tests and can work with you to find your path to wellness.



Ankri, S. (2015). Entamoeba histolytica – tumor necrosis factor: a fatal attraction. Microb Cell, 2(7), 216-218. doi:10.15698/mic2015.07.216

Carneiro, F. S., Webb, R. C., & Tostes, R. C. (2010). Emerging role for TNF-alpha in erectile dysfunction. J Sex Med, 7(12), 3823-3834. doi:10.1111/j.1743-6109.2010.01762.x

Yang, S. N., Hsieh, C. C., Kuo, H. F., Lee, M. S., Huang, M. Y., Kuo, C. H., & Hung, C. H. (2014). The effects of environmental toxins on allergic inflammation. Allergy Asthma Immunol Res, 6(6), 478-484. doi:10.4168/aair.2014.6.6.478

Zhang, J. M., & An, J. (2007). Cytokines, inflammation, and pain. Int Anesthesiol Clin, 45(2), 27-37. doi:10.1097/AIA.0b013e318034194e


Microbiome & Immune Connection


Microbiome and the Influence on the Immune System-it’s more important than you think!

The composition of the microbiome can influence the function of your IMMUNE SYSTEM.  For example, numerous studies indicate that your microbiome can influence  your susceptibility to certain bacteria such as Campylobacter, which is often seen in anxiety disorders.  In fact, a book by Martin Blaser called “Missing Microbes” discusses that the alteration of the human microbiome could be one of the factors attributed to the rise of conditions such as food allergies, asthma, celiac disease and intestinal disorders such as IBD.  His theory is that the modern medical practices, that includes overuse of antibiotics, may have negatively shifted the microbiome in a way that is affecting human health detrimentally.  The use of antimicrobial drugs is known to be associated with the development of certain infectious diseases, such as colitis and candida overgrowth, through disruption of this delicate microbiome balance (Casadevall and Pirofski, 2018).

It is hypothesized that the establishment of your microbiome occurs during the first 3 years of your life, and disruptions in this establishment during this time can have long term implications (Blaser, 2016).  According to Blaser, 50% of babies in the US are born by C-section, and this can be the beginning of some of the various disruptions in the delicate microbiome balance. This is not limited to bacteria, but also fungal and viral elements of the microbiome, that are also demonstrating a role in human health as well.

Nutritional intervention: Probiotics
A nutritional intervention to address the microbiome is the use of probiotics.  Probiotics are live organisms that, when ingested in adequate quantities, exert a health benefit on the host.  Probiotics can directly stimulate the growth of beneficial bacteria and competitively exclude the number of more harmful, toxin producing microbiota (Zhou & Foster, 2015).  Lactobacillus, Bifidobacterium, and Saccharomyces are three extensively studied and commonly used probiotics in humans and animals.

Probiotics are demonstrating to directly affect your gut immune system, which is responsible for

Three main beneficial effects of probiotics on your gut defense system include the following:

  1. Probiotics can block pathogenic bacteria by producing substances that directly compete with pathogens for adherence to the intestinal epithelium.
  2. Probiotics can enhance intestinal barrier function and stimulate protective responses from epithelial cells. This can lower the chance of bacteria translocating into the blood stream and entering systemically. This function may decrease infections and immune related reactions, thus supporting the health of the immune system (Enviormedica, n.d).
  3. Probiotics are able to modulate the immune system and pathogen induced inflammation through various immune regulated signaling pathways.

Immune Cells

Probiotics can regulate host innate and adaptive immune responses by modulating the functions of your very immune cells.    For example, a probiotic mixture consisting of L. acidophilus, L. casei, L. reuteri, B. bifidium, and Streptococcus thermophilus stimulated regulatory proteins involved in your immune system that are responsible for both inflammatory and anti-inflammatory mechanisms.

Intestinal Epithelial Cells

Probiotics can repair damaged epithelial barrier while producing antibacterial substances and protective proteins, as well as regulate intestinal epithelial immune function (such as cytokine production) (Yan & Polk, 2011).  For example, l. johnonsii has the ability to upregulate various receptors on your immune cells,  which may indicate that the probiotic is able to stimulate the gut immunity. “These findings suggest that probiotics regulation of innate immunity in intestinal epithelial cells may serve as a mechanism for disease prevention and treatment” (Yan & Polk, 2011).


American Society for Microbiology. (2016, September 6).  Missing Microbes with Dr. Martin Blaser.  Retrieved 2018, May 4 from

Environmedica. (n.d.). Probiotics for Immune System Support. Retrieved 2018, May 3 from (Links to an external site.)Links to an external site.

Yan, F., & Polk, D. B. (2011). Probiotics and immune health. Curr Opin Gastroenterol, 27(6), 496-501. doi:10.1097/MOG.0b013e32834baa4d

Zhou, L., & Foster, J. A. (2015). Psychobiotics and the gut-brain axis: in the pursuit of happiness. Neuropsychiatr Dis Treat, 11, 715-723. doi:10.2147/ndt.S61997