THE TRUTH ABOUT D
In cases when whole populations are given large amounts of vitamin D, the only ones who remain “deficient” appear to be those whose immune systems are fighting disease. Could these people be actively downregulating active vitamin D in favor of the inactive form? Could low vitamin D levels be a biomarker for other imbalances?
“Homeostatic regulation” means that hormones such as 25-D work in cooperation with other hormones, substrates, ligands, enzymes, bacteria, minerals, receptor sites, energy, etc. Like any hormone, it has both an active and an inactive form, in order to up-regulate or down-regulate the immune system to adapt to its environment. Chronic disease is “multifactorial with many pleomorphic, intracellular species involved. The various species can work in concert and may have even mutated specifically for the host by sharing genetic information by horizontal transfer of DNA.”
PART II: THE TWO FACES OF VITAMIN D
Studies show the action of vitamin D to be biphasic, with a stimulatory effect at lower concentrations, and becoming more inhibitory or ineffective at higher levels. In the same way autoimmune disease responds to corticosteroid (Prednisone) treatment, vitamin D can temporarily reduce symptoms of disease, but long-term use appears to dramatically increase the odds of disease relapse.
For example, when excess D is supplemented, cells respond by reducing the number of receptors thereby downregulating the system, or alternatively cells become more receptive to the inactive form of the hormone. If there is a shortfall of vitamin D, the cells will increase the number of receptors, thereby upregulating the system and become more sensitive to the uptake of active hormone. In the case of vitamin D, supplementing with too much active D may actually suppress the immune system as levels of the inactive form increase.
LESS IS MORE
Vitamin D action is complex, but also intuitive. In light of contradictory evidence and shifting views, science should never ignore the alternative hypothesis. Science must question the answers. Instead of rationalizing the data it may be time to reexamine the model.
The true model of the vitamin D feedback system is self-regulating. A self-regulating system monitors itself; no outside assistance necessary. When the VDR receptor is activated, it transcribes the gene (CYP24A1) for the P450 enzyme that inactivates 1,25-D. This downregulation maintains homeostasis to limit the concentration of 1,25-D to just that amount needed for proper transcriptional activation of the VDR.
When excess 25 D is taken in through supplementation, high levels of D can disrupt natural communication in the feedback system by allowing the creation of unrequested active 1,25D. Active vitamin D, in the presence of no open VDR receptors, binds to other receptors: such as the thyroid, cortisol, and testosterone receptors to create hormonal imbalances. Enzymes in tumor cells can work overtime to break down vitamin D to limit survival in cancer cases.
When observing patients with autoimmune disease, inactive 25-D, lacking one hydroxyl group, can block the VDR gene. Researcher, Paul Albert says, “As its concentration builds, 25-D inactivates VDR expression. This means that supplementing stifles rather than activates transcription and immune function.
According to researcher Trevor G Marshall, inactive “25-D levels are naturally downregulated by the disease process itself – a process driven by the ability of chronic, intracellular metagenomic pathogens to create VDR-blocking ligands.”
In other words, “lower average levels of vitamin D frequently observed in autoimmune disease are not a sign of deficiency. Instead, it is proposed that the lower levels result from chronic infection (known as Th1 illnesses) with intracellular bacteria (known as Th1 pathogens) that dysregulate vitamin D metabolism by causing vitamin D receptor (VDR) dysfunction within phagocytes.”
Why are women diagnosed with 78% of autoimmune disease? Some reasons include:
women produce stronger humoral and cellular immune responses to antigen than males (Ansar Ahmed et al., 1985).females produce higher levels of CD4 + T cells in response to immunization (Ho et al., 1995).
women produce higher levels of circulating antibodies than men (Rowley and Mackay, 1969), which could underlie their propensity to produce higher levels of autoantibodies in autoimmune diseases (Whitacre et al., 1999).
women show increased immune reactivity (Hewagama et al., 2009), and this greater immunocompetence may translate to greater resilience to infectious and some non-infectious diseases. However, it is possible that this greater immune reactivity makes women more prone to developing autoimmune disease (Zandman-Goddard et al., 2007).
GOT LEAKY GUT?
We are 10:1 more bug than human cells. We are microbiome (bacteria) and at least 10% virome (virus). We are yeast. Sometimes we are parasites. Our microbiota evolves right along with us. In high numbers, they produce ligands that bind and inactivate the gene (VDR) which encodes the nuclear receptor for vitamin D3. It is our microbes and their byproducts that drive disease and health.
VDR is found in all immune cells all over the body. When ligands from pathogens bind to the VDR gene, they downregulate active vitamin D and block its transcription for more. Opportunistic bacteria, yeast, and fungus, and their toxic byproducts (biotoxins), create an environment that benefits them. The cells release cytokines that cause inflammation, which under chronic conditions, can lead to tears in the lining of the small intestine, which can lead to autoimmunity. Inflammation of the gut penetrates the brain through the gut-brain axis. A cascade reaction begins as chronic inflammation snowballs expands to affect organ systems and pathways to appear that one autoimmune disease snowballs into others.
Like us, our microbes survive to thrive. They live under the law of Pleomorphism whereby if the conditions of the terrain (microbiome) change, so do they. As shapeshifters, they persist and reproduce by disabling the innate immune response.
Therefore, building gut integrity to close the gaps can restore innate immunity for the host. Innate immunity is made up of your mucosal epithelia (skin, airway, reproductive tract, and intestine), the main interface between us and the microbial world (including both pathogenic and symbiotic microbes). At this level are natural defenses which include the gut associated lymphoid tissues, with Peyer’s Patches, T-cells, macrophages, neutrophils, etc. Heal the gut, heal the immune system.
Even in light of new evidence, the beauty of sun-loving, self-sustaining vitamin D continues to be ignored by the mainstream. So the concept of vitamin D “deficiency” continues unabated by medical and natural doctors, alike, who push vitamin D supplementation without addressing the true cause. And disease statistics escalate. It’s clear that this trend can only be remedied by a rise in independent thinking.
PART III: THE STUDIES
“The term intraphagocytic refers to the fact that these bacteria have developed the ability to remain alive and proliferate undetected inside the cytoplasm of the cells they infect. These cells include macrophages, the very cells of the immune system that the body uses to kill invading pathogens. Once inside these cells, they cause our own cells to release inflammatory cytokines (proteins that often generate pain and/or fatigue).” It is the “cytokine storm” that summon and cause the creation of macrophages.
VITAMIN D AND YEAST INFECTION
One of vitamin D’s roles is to produce an anti-microbial peptide called cathelicidin, a critical component in the lysosomes of macrophages, in leukocytes, and in keratinocytes to fight off bacterial infection, as well as Candida (yeast). VDR also transcribes TLR2, needed for macrophages to detect an internal infection, within themselves.
For example, sarcoidosis is an inflammatory disease that infects the phagocytes of the immune system. It has a bacterial pathogenesis. More specifically, it is a cytoplasmic microbiota of intraphagocytic, L-form bacteria that seems to drive the biochemical changes observed in sarcoidosis, because it responds to antibiotics. Therefore, reversing bacteria-induced D-receptor dysfunction is key for sarcoidosis and all autoimmune disease. A number of autoimmune diseases can be reversed by gradually restoring VDR function with the VDR agonists which, from the medical community, have included certain bacteriostatic antibiotics.
However, Nature has her own solution. “When the immune system is challenged by injury or pathogens, TGF-beta and/or interferon-gamma are released, additional CYP27B1 is generated, and thus additional (active) 1,25-D In turn, the VDR is activated to express more antimicrobial peptides (cathelicidin and beta-Defensin-2). Additionally, when the VDR is activated, TLR2 is expressed, allowing the immune system to recognize gram-positive bacteria, including Staphylococcus aureus, Chlamydia pneumonia, and Mycoplasma pneumoniae.”
A study published in the Journal of Infectious Diseases found both a positive and negative relationship between different doses of vitamin D and Candida infection. In mice, low doses of activated vitamin D reduced fungal burden and led to improved survival compared to mice not given activated vitamin D. However, high doses of activated vitamin D led to poor outcomes in the mice. Researchers concluded, “Mechanistically, low dose (activated vitamin D) induced proinflammatory immune responses. These beneficial effects were negated with higher vitamin D doses.”
VITAMIN D AND CARDIOVASCULAR DISEASE
A 2013 study in the American Journal of Cardiology found an inverse relationship between vitamin D and C-Reactive Protein (a factor linked to stiffening of the blood vessels and increased risk of artherosclerosis). Researchers concluded, “The inflammation that was curtailed by vitamin D does not appear to be curtailed at higher levels of vitamin D”. “The inverse relation between vitamin D supplementation and inflammatory biomarkers among asymptomatic adults is not settled.”
“Clearly vitamin D is important for heart health, especially if you have low blood levels of vitamin D. It reduces cardiovascular inflammation and atherosclerosis, and may reduce mortality, but it appears that at some point it can be too much of a good thing.” Study leader Muhammad Amer advised caution in supplementation. “Those pills could have unforeseen consequences to health even if they are not technically toxic.” Note: Each 100 international unit of vitamin D ingested daily produces about a one nanogram per milliliter increase 25-Hydroxyvitamin D levels in the blood.
A similar relationship was found between activated D and homocysteine levels with a positive relationship when vitamin D stayed below 21 ng/L and a negative relationship above 21 ng/L. Hyperhomocysteinemia is an independent risk factor for premature atherosclerosis and thromboembolism.
Again, we see that increasing levels of the active form 1,25-D do not always solve an inflammatory problem. Like nature, everything strives for balance while interacting with its environment, including vitamin D steroid hormone.
Recall that researchers have made similar misjudgments regarding the relationship between cholesterol and heart disease, only in reverse. When looking at the broader picture, it becomes clear that cholesterol (like 1,25-D) is a biomarker, not a cause of disease. Cholesterol protects against atherosclerosis and infections. People with high cholesterol (not low) actually live longer.
VITAMIN D AND OSTEOPOROSIS
Active 1,25-D increases blood calcium levels by increasing the uptake of calcium from the gut into the blood. So high serum levels of D absolutely require higher levels of calcium. When dietary sources of calcium are exhausted the body takes it from the bone, resulting in osteoporosis. This process exhausts the telomeres that create the osteoclasts and osteoblasts constantly required to maintain these high D levels.
Extra calcium can precipitate in arteries and on the outside of the bones, causing arteriosclerosis and bone-deformities. It can also settle in joints and ligaments, and can cause muscle-cramps because the blood-calcium level needs to be low enough to deport calcium from muscle cells. It can also kill muscles cells (if the calcium cannot be deported), eventually causing fibromyalgia. Might the high serum levels of Ca (from supplementation) explain the calcification diseases seen today? Like other chronic diseases, osteoporosis is often accompanied with a very low vitamin D level.
Hypercalcemia is the most common life-threatening metabolic disorder associated with neoplastic diseases, occurring in an estimated 10% to 20% of all adults with cancer. Solid tumors (such as lung or breast cancer tumors) as well as certain hematologic malignancies (particularly multiple myeloma) are most frequently associated with hypercalcemia.
Primary hyperparathyroidism is the most common cause of hypercalcemia, due to excess Parathyroid hormone (PTH) release by the parathyroid glands. Therefore, since both vitamin D and parathyroid hormone help manage calcium balance in the body it is beneficial to look at PTH as an indicator of bone health because vitamin D supplementation can also lower serum PTH which can lead to osteomalacia, bone loss, and increased risk of fracture.
EXCESS VITAMIN D AND HYPOTHYROIDISM
The thyroid gland is typically the first victim of excess 1,25-D because it will park in the thyroid receptor. A poorly functioning thyroid is often the result T4 hormone not converting into the bioactive hormone, T3, but instead converting into the inactive rT3 (reverse tri-iodothyronine) hormone. As rT3 levels increase, T3 levels fall (hypothyroidism) metabolism and body temp decreases, and various enzymes fail to function properly. In addition, elevated cortisol due to adrenal dysfunction can contribute to this faulty conversion.
The pattern to select for inactive thyroid hormone at the receptor site is the same pattern for vitamin D metabolism. According to several studies, vitamin D-deficiency is linked to changes in the VDR, vitamin D-binding protein, and enzymes when thyroid autoantibodies are present. Different alleles are affected between Hashimoto’s and Graves and also between different cultural groups. Both thyroid hormone and vitamin D hormone metabolism appear to downregulate in response to inflammation caused by a shift in our microbes at the level of the gut.
VITAMIN D AND CANCER
Research shows a link between high levels of bioavailable, circulating inactive 25-D and pancreatic cancer risk. One study suggests it may be valuable to look at levels of D-binding protein (DBP) and inactive 25-D in determining cancer risk since it is thought that higher DBP concentrations may sequester more 25-D and reduce free 25-D bioavailability. All tolled about 1% of 25-D circulates freely while 10-15% is bound to albumin – it is this combined fraction of vitamin D that is considered bioavailable or “free25-D.” Note: albumin found in vaccines may further interfere with levels of free 2-5-D.
Another parameter to monitor is the nagalase enzyme. This enzyme sabotages vitamin D-binding protein, also known as GcMAF, or Gc. Gc is converted into GcMAF, by a combination of B and T immune cells. GCMAF then activates the immune system by its binding to macrophages and vitamin D. Cancer cells and viruses release biotoxins, including the nagalase enzyme which splits apart the protein Gc-MAF.
When nagalase splits Gc-MAF, it binds to the Gc protein and thereby prevents macrophages, and vitamin D from binding to it. When Gc protein cannot be converted to GcMAF the entire immune system is disabled. Nagalase spreads with impunity. One nagalase enzyme molecule can destroy a large quantity of GcMAF molecules. With no natural enemies (except radiation and chemotherapy, which destroys the immune system), only the addition of GcMAF protein in the body can reactivate the immune system.
Nagalase enzyme can also be used as a tool to track the rise or fall of cancer in the body. Many doctors who understand this relationship have successfully used GcMAF therapy over a six month course to reverse cancer and autoimmune disease. The protocol recommends 100 ng GcMAF intramuscular injections. Monthly Nagalase level tests follow the Nagalase level as it reverts back to baseline. Allopathic medicine has yet to embrace nagalase as a measure of cancer reversal since they are forever looking for a cure. Measuring nagalase enzyme in patients with prostate cancer administered GcMAF immunotherapy showed complete tumor reversal and no recurrence for seven years.