Dr. Joseph M. Miller DO

ROOT Cause Supplements, LLC

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Body Fat and Inflammation Affect Colon Cancer Outcomes

Results from a multicenter study

Study Objective

To evaluate the association between body composition and related inflammatory biomarkers with 5-year survival in patients with nonmetastatic colon cancer

Design

A prospective, multicenter, translational cohort study using a retrospective placebo comparison group

Participants

All participants included in the study were diagnosed with nonmetastatic colon cancer without underlying chronic inflammatory conditions. These patients were not treated with anti-inflammatory medications.

All participants underwent elective resection for colon cancer with curative intent.

Study Parameters Assessed

After initial diagnosis, all patients were staged, and metastasis was ruled out using standard imaging guidelines. Patients were followed with active surveillance for 5 years, which included measurement of carcinoembryonic antigen (CEA), colonoscopy, and imaging studies.

Blood samples were collected from patients preoperatively.

White blood cell count and albumin levels were analyzed. Acute phase protein and cytokine levels were measured and included interleukin 1b (IL-1b), IL-2, IL-10, C-reactive protein (CRP), tumor necrosis factor (TNF)-alpha, and vascular endothelial growth factor (VEGF).

CT studies measured total fat area and subcutaneous fat area. Calculations for visceral-to-total fat ratio and subcutaneous-to-total fat ratio were made.

CT studies were also used to measure skeletal muscle area (SMA).

The association of body composition profiles with 5-year cancer recurrence and disease-specific mortality were analyzed using Mantel Cox log-rank test, and Kaplan-Meier curves were produced.

When specific composition profiles were significantly associated with poor clinical and cancer outcomes, comparison of mean inflammatory mediator expression levels was performed using the Mann-Whitney U test.

Primary Outcome Measures

Associations of body composition profiles with 5-year cancer recurrence and disease-specific mortality

Key Findings

Overall low skeletal muscle area (SMA) and high visceral-to-total fat ratio were significantly associated with less favorable clinical and cancer outcomes.

Low SMA was associated with a more than 2-fold increase in recurrence of colon cancer in the 5-year postsurgical period (low SMA: hazard ratio [HR], 2.30 [95% CI, 1.41–2.89]; P=0.04).

High visceral-to-total fat ratio was significantly associated with developing a cancer recurrence within the first 5 years after surgery (high visceral-to-total fat ratio: HR, 5.78 [95% CI, 3.66–7.95]; P=0.02).

Low SMA (OR, 2.13 [95% CI, 1.85–5.36]; P=0.004) and high visceral-to-total fat ratio (OR, 3.20 [95% CI, 1.85–10.84]; P=0.01) were significantly associated with developing a 30-day infective complication.

High visceral-to-total fat ratio was the only body composition profile significantly associated with cancer-related mortality within the first 5 years after surgery (HR, 5.92 [95% CI, 4.04–8.00]; P=0.02). There was no significant association between low SMA and 5-year disease-specific mortality.

Patients with low SMA who developed cancer recurrence, compared with those who did not, had significantly higher levels of CRP, VEGF, and CD14 expression.

Patients with high visceral-to-total fat ratio who developed recurrence, compared with those who did not, had higher levels of IL-6 (mean [SD], 5.26 [7.05] ng/mL vs 2.76 [3.11] ng/mL; P=0.03) and TNFα (mean [SD], 5.74 [4.53] ng/mL vs 4.50 [1.99] ng/mL; P=0.03).

Practice Implications

This study showed an association between visceral fat and poorer outcomes, which is not surprising. There is an accumulation of literature showing that visceral fat is a risk factor for cardiovascular diseases, type 2 diabetes, breast cancer, and other chronic conditions.¹ This study also demonstrated the relationship between visceral fat and measurable inflammatory mediators in the blood. In other studies, increased visceral fat has been associated with the increased release of free fatty acids into portal circulation, which results in insulin resistance and other metabolic syndromes.² Conversely, subcutaneous fat correlated with increased levels of IL-2 and IL-10, cytokines thought to possess predominantly anti-inflammatory effects.

The World Cancer Research Fund International lists 10 established obesity-related cancers, including postmenopausal breast, endometrial, ovarian, advanced prostate, colorectal, renal, pancreatic, liver, and gallbladder cancers and esophageal adenocarcinoma.³ Clearly, obesity needs to be addressed as 1 of the strategies in approaching these obesity-related cancers. However, we must be mindful of how body fat is being assessed in our evaluation and assessment of individuals.

Body mass index (BMI), though recommended as an index of obesity and disease risk, has its limitations. It is nonspecific, with only the weight and height used to calculate BMI. There is no differentiation of muscle mass or any delineation of visceral versus subcutaneous fat.⁴ Therefore, BMI cannot predict the risks associated specifically with elevated levels of visceral fat.

This phenomenon is referred to as the ‘obesity paradox’ and is well-recognized in the cardiometabolic literature but less so in oncology.

 

The common perception is that excess adiposity, approximated by BMI, is associated with reduced cancer survival. However, several studies have demonstrated that overweight and early obese states are associated with improved survival. This phenomenon is referred to as the “obesity paradox” and is well-recognized in the cardiometabolic literature but less so in oncology.³ This suggests that BMI is not a reliable form of measurement or prognostic tool due to its inability to evaluate fat deposition, particularly subcutaneous vs visceral fat.³

Waist-to-hip ratio (WHR) may be a better tool to consider when evaluating patients who may be at increased risk for colon cancer recurrence or morbidity related to colon cancer. WHR was found to be a better anthropometric measurement compared to measuring waist circumference alone or BMI, for assessing excess levels of visceral fat.⁵

Increased levels of subcutaneous fat and low skeletal muscle area (SMA) were associated with increased levels of inflammatory mediators (ie, IL-6, CRP, VEGF), which are known to promote cancer cell survival and metastatic transformation.

Researchers have questioned whether targeted anti-inflammatory therapies that work to inhibit IL-6 and other inflammatory mediators have a role in modulating the inflammatory association of body composition with cancer outcomes. Perioperative use of taurolidine, a taurine derivative, significantly diminished circulating IL-6 levels for the first 7 days following surgical resection in nonmetastatic colon cancer.⁶ Taurolidine has been shown to inhibit pro-inflammatory cytokines, specifically TNF-alpha and IL-6.⁷ Whether taurolidine affects outcomes was not part of that study’s design.

Given the apparent role that high systemic inflammation plays in poorer outcomes for cancers, an anti-inflammatory dietary approach should be considered. A 2006 study observed an inverse association between fruit and vegetable intake and CRP.⁸ Diets high in dietary fiber and rich in fruits and vegetables are associated with lower CRP levels, while consumption of a Western diet, high in fat, sugar, sodium, and refined grains, has been correlated with elevated CRP levels.⁹ A 2004 study found that adhering to a Mediterranean diet (rich in olive oil, fish, nuts, seeds, fruits, and vegetables) lowered CRP levels by an average of 20 percent.¹⁰

Sleep hygiene and exercise can also be included as part of a strategy to address concerns of higher systemic inflammation. CRP, IL-6, and fibrinogen have been linked to sleep, with higher levels of these markers associated with poorer sleep.¹¹ More active individuals involved in regular exercise have lower concentrations of IL‑6 and CRP.¹²

The study reviewed here found unfavorable outcomes in nonmetastatic colon cancer associated with body composition and increased expression of proinflammatory pathways. These are important points that should be acknowledged and addressed in the clinical setting. However, it is important to note that this was a small cohort study involving only 28 patients. In addition, men comprised 78.6% of the study participants, compared to women at 21.4%.

 

 

PANS Blog # 0067 – November 2, 2023

 

 

PANS (Pediatric acute-onset neuropsychiatric syndrome) currently is characterized as a Pediatric Autoimmune Neuropsychiatric disorder, has different presentations, and most probably several causes / etiologies.

As with all disorders, there is no black and white in medicine, mostly gray. The Autoimmune trigger / dysregulation could result from a viral syndrome / episode (Streptococcal, HSV viruses, Influenza, RSV, COVID etc…). It could be a result of a genetic predisposition, with a trigger to manifest the Syndrome Clinically. Environmental and Food Sensitivities may also play a role, causing a release of Histamine and other inflammatory compounds such as cytokines and leukotrienes and resultant Immune System Dysfunction.

Inflammation has an impact on every individual in a unique way. We all have unique GUT Microbiomes and unique Immune systems. Just as we all have different fingerprints, we all have different blueprints for our Immune Systems and GUT Microbiome.

Thus, Inflammation affects us in similar ways with Joint Pain, Headaches, Sinusitis etc., it also affects us differently when it comes to Autoimmune disorders.  

Lowering Inflammation (Oxidative Stress = Chronic Inflammation on our Cells, Tissues, and Organs), consistently on a daily basis; with pure plant-based supplements without fillers, preservatives or anti-caking agents is extremely beneficial long-term for individuals with autoimmune disorders.

The Purity of the supplement is extremely important as fillers, preservatives and anti-caking agents can defeat the purpose of taking them to decrease inflammation, as these agents can create a low- level inflammatory response.

Therefore, lowering inflammation consistently on a daily basis, with pure plant-based compounds, in synergistic capsule formulas; where all ingredients are delivered to the small intestine and released from the capsule together, is very important to achieve a desired Therapeutic / Clinical Positive Response. The ingredients of the capsule being together at the time of absorption in the small intestine is crucial, as ALL the ingredients in our capsules (ROOT Cause Supplements) have a purpose to promote superior absorption and bioavailability.

We only source organic plant-based ingredients, and the vitamins and minerals such as  Vitamin D3, Zinc etc. are PURE and Professional-Grade.

Our Curcu-Meric 975mg capsule versions .001 & .002 is our Flagship Capsule, and the starting point for individuals looking to reduce their whole-body Inflammation; whether it be to Treat / Prevent Autoimmune disorders, Cardiovascular disease, Neurologic / Brain Health decline, Intestinal / Colon Problems, Arthritis and joint Pain, Liver and kidney disease, Endocrine and Hormone Imbalances.

Starting with Curcu-Meric 975mg, our capsules all work synergistically with Crucu-Meric to Address “The ROOT Cause” of medical disorders, and prevent disease onset while improving quality of life.

 

ROOT Cause Supplements, Fort Lauderdale, FL

Owner / CEO / Biochemist – Dr. Joseph M. Miller DO

 

Immune System 0011

Dr. Joseph M. Miller DO

 

The main parts of the immune system are:

 

• white blood cells
• antibodies
• complement system
• lymphatic system
• spleen
• bone marrow
• thymus

White blood cells

White blood cells are the key players in your immune system. They are made in your bone marrow and are part of the lymphatic system. 

White blood cells move through blood and tissue throughout your body, looking for foreign invaders (microbes) such as bacteria, viruses, parasites and fungi. When they find them, they launch an immune attack. 

White blood cells include lymphocytes (such as B-cells, T-cells and natural killer cells), and many other types of immune cells.

Antibodies

Antibodies help the body to fight microbes or the toxins (poisons) they produce. They do this by recognizing substances called antigens on the surface of the microbe, or in the chemicals they produce, which mark the microbe or toxin as being foreign. The antibodies then mark these antigens for destruction. There are many cells, proteins and chemicals involved in this attack. 

 

 

 

 

Complement system

The complement system is made up of proteins whose actions complement the work done by antibodies. Typically, we measure C3, C4, CH50 levels to help confirm the if someone has immune deficiencies.

Lymphatic system

The lymphatic system is a network of delicate tubes throughout the body. The main roles of the lymphatic system are to:

• manage the fluid levels in the body
• react to bacteria
• deal with cancer cells 
• deal with cell products that otherwise would result in disease or disorders
• absorb some of the fats in our diet from the intestine. 

The lymphatic system is made up of:

• lymph nodes (also called lymph glands) -- which trap microbes
• lymph vessels -- tubes that carry lymph, the colorless fluid that bathes your body's tissues and contains infection-fighting white blood cells
• white blood cells (lymphocytes).

Spleen

The Spleen is a blood-filtering organ that removes microbes and destroys old or damaged red blood cells. It also makes disease-fighting components of the immune system (including antibodies and lymphocytes).

Bone marrow

The Bone Marrow is the spongy tissue found inside your bones. It produces the red blood cells our bodies need to carry oxygen, the white blood cells we use to fight infection, and the platelets we need to help our blood clot. 

 

Thymus

The thymus filters and monitors your blood content. It produces the white blood cells called T-lymphocytes.

 

 

 

Humoral (B-Cell) and Cell-Mediated (T-Cell) Immune Responses

The immune system distinguishes two groups of foreign substances. One group consists of antigens that are freely circulating in the body. These include molecules, viruses, and foreign cells. A second group consists of self-cells that display aberrant MHC proteins. Aberrant MHC proteins can originate from antigens that have been engulfed and broken down (exogenous antigens) or from virus‐infected and tumor cells that are actively synthesizing foreign proteins (endogenous antigens). Depending on the kind of foreign invasion, two different immune responses occur:

The humoral response (or antibody‐mediated response) involves B cells that recognize antigens or pathogens that are circulating in the lymph or blood (“humor” is a medieval term for body fluid). The response follows this chain of events:

 

 

1.    Antigens bind to B cells.

2. Interleukins or helper T cells co-stimulate B cells. In most cases, both an antigen and a co-stimulator are required to activate a B cell and initiate B cell proliferation.
3. B cells proliferate and produce plasma cells. The plasma cells bear antibodies with the identical antigen specificity as the antigen receptors of the activated B cells. The antibodies are released and circulate through the body, binding to antigens.
4. B cells produce memory cells. Memory cells provide future immunity.

 

The cell‐mediated response involves mostly T cells and responds to any cell that displays aberrant MHC markers, including cells invaded by pathogens, tumor cells, or transplanted cells. The following chain of events describes this immune response:

 

1.    Self-cells or APCs displaying foreign antigens bind to T cells.

2. Interleukins (secreted by APCs or helper T cells) co-stimulate activation of T cells.
3. If MHC‐I and endogenous antigens are displayed on the plasma membrane, T cells proliferate, producing cytotoxic T cells. Cytotoxic T cells destroy cells displaying the antigens.
4. If MHC‐II and exogenous antigens are displayed on the plasma membrane, T cells proliferate, producing helper T cells. Helper T cells release interleukins (and other cytokines), which stimulate B cells to produce antibodies that bind to the antigens and stimulate nonspecific agents (NK and macrophages) to destroy the antigens.

 

 

 

 

 

Dr. Joseph M. Miller DO

 

Auto-Immune disorders have been a focal area of research for me over the past 15 years. As an Obstetrician / Gynecologist, I have encountered many patients with Auto-Immune Disorders. Women have a higher prevalence of Auto-Immune disorders due to 2 primary factors. 1- monthly cyclic fluctuations in Hormones, which place a burden on the Immune System; 2- Child Birthing Process.

Overall, we have seen a significant increase in auto-immune disorders in both men and woman, secondary to an increased bombardment on our Immune Systems. Increasing Environmental Toxins and chemicals, along with increased exposure to unhealthy ingredients in our food sources; excess Societal and Emotional stress, Workplace chemicals and toxins, all contribute to a significantly increased inflammatory burden on our CELLS and IMMUNE SYSTEM.

This spectrum of disorders, the majority of which are categorized as Connective Tissue Disorders, have a wide range of presentations. Most women present with non-specific symptoms, most commonly arthritis, swelling & fatigue. Arthritis most commonly presents in the hands, and is worse during the morning hours, with reported improvement when placing their hands under warm water.

Simply by history alone, any young woman with complaints of arthritis, without any history of trauma or repetitive wear and tear injury to the affected area, can be assumed to be dealing with an Inflammatory Arthritis, which is Immune System related, versus Osteoarthritis, which originates from injury or wear and tear (Old Age). Meaning, the Immune System is attacking certain connective tissues, starting in the smaller joints of the hand, wrist, elbow, or ankle, with associated swelling, and is usually bilateral.

Initial laboratory testing may be normal. In this case, they are referred to as Sero-Negative Arthritis. This is a very common presentation. In other cases, we may see an elevation in non-specific inflammatory markers such as ESR, CRP, RF Factor, WBC count, specifically lymphocytes and/or eosinophils. If an ANA titer is positive, testing for specific anti-bodies which are more indicative of a specific disorder: Lupus, Rheumatoid Arthritis, Sjogren’s, Scleroderma, Psoriatic Arthritis, MS, UC etc.., is the next step.

Key point is whether you are dealing with early-stage Auto-Immune Inflammatory Condition, or a later stage, and/or more aggressive specific syndrome, the treatment is the same. The causative pathology is the same. The Immune System has been over-worked and burdened for years, from many causes, some of which are described above. Thus, the Immune System reacts aberrantly in an overzealous fashion. Treatments revolve around suppressing inflammation and suppressing the Immune System Response.

Yes, Corticosteroids are very useful, however, they have many serious long term side effects. Therefore, they are usually given in short weaning protocols during acute flares. NSAIDS, such as Ibuprofen, Advil, Aleve, and the prescription NSAIDS are helpful to relieve the pain, however, once again have long term adverse effects on the Gut, Heart, Kidneys and Liver. Both these treatments are not addressing the ROOT Cause of the underlying problem.

The Immune-System is normally programmed to perform by responding to external agents such as Viruses, Bacteria and other pathogens, as well as initiate a repair and heal response once an injury occurs. When the Triggering event or agent has been around for prolonged periods of time, the Immune System becomes over-worked and can be triggered to respond aberrantly and become dysregulated. Most Individuals don’t realize their Immune-System is being overworked until they manifest signs and symptoms.