More on Vitamin D, Ergosterol and Cholesterol

Do Vitamin D Levels Affect Cholesterol?

~Content Source

Higher vitamin D levels appear to be associated with higher total cholesterol levels and higher HDL cholesterol levels, according to a new study presented at the American College of Cardiology’s (ACC) 65th Annual Scientific Sessions.1 

Investigators looked 13 039 adults and found that higher 25-hydroxyvitamin D (25[OH]D) was cross-sectionally and prospectively associated with higher total cholesterol and HDL cholesterol levels and lower total cholesterol-to-HDL cholesterol ratio after considering factors such as diabetes and adiposity.

“We wanted to see the association of low vitamin D with low HDL cholesterol and high total cholesterol-to-HDL cholesterol ratio, but I think we were most surprised to not find an association of vitamin D deficiency with elevated triglycerides, as has been noted in other studies. This may be in part that we carefully adjusted for other confounding lifestyle variables such as physical activity and 2 measures of adiposity (BMI and waist circumference),” said senior study author Erin Michos, MD, MHS, associate professor of medicine and epidemiology and associate director of preventive cardiology at Johns Hopkins School of Medicine in Baltimore.

“We also were surprised that we did not see any association of low vitamin D with elevated LDL cholesterol in our overall sample. However, when we performed a sensitivity analysis looking at individuals who were not taking lipid-lowering therapy at the baseline exam or at any of the follow-up visits, we did see the association of low vitamin D with elevated LDL cholesterol.”

Dr Michos and her colleagues measured lipids at baseline (1990-1992), in 1993-1994, and in 1996-1998. The mean follow-up was 5.2 years.

The investigators used linear and mixed model regression methods to assess associations of 25(OH) D with cross-sectional and lipid trends. They also adjusted for clinical characteristics. The mean age at baseline was 57.6 years, 57% were women, and 24% were black.

Among those individuals without baseline dyslipidemia, participants with low 25(OH) D (<20 ng/mL) compared with optimal levels (≥30 ng/mL) had increased risk for incident dyslipidemia in demographic-adjusted models (hazard ratio [HR]=1.19; 95% CI, 1.02-1.39). Nevertheless, this finding was attenuated in fully-adjusted models (HR=1.12; 95% CI, 0.95-1.32).1

Dr Michos said low concentrations of vitamin D, defined as serum 25(OH)D below 30 ng/mL, are present in more than two-thirds of the US adult population and in an estimated 1 billion individuals worldwide. 

“So, this is a major relevant public health issue. Vitamin D deficiency has been associated with a number of non-bone-related adverse health outcomes, including increased risk for cardiovascular diseases (CVDs). One of the mechanisms by which vitamin D may influence CVD risk is through an effect on lipids,” Dr Michos told Endocrinology Advisor. “The potential link between vitamin D deficiency and adverse lipid profile should be of great interest to a large number of practitioners who treat both vitamin D and lipid disorders, including endocrinologists, internists, lipidologists, and cardiologists.”

Previous studies, including one study conducted by her team and recently published in the Journal of Clinical Lipidology, suggested that low levels of vitamin D were associated with an atherogenic lipid profile consisting of elevated LDL cholesterol, elevated triglycerides, and lower HDL cholesterol, noted Dr Michos.2 However, most of the evidence supporting this association was obtained in cross-sectional analyses. 

For this current investigation, the researchers analyzed the association between vitamin D status and the lipid profile prospectively using data from the Atherosclerosis Risk in Communities (ARIC) study. This large study of a US community-based sample of blacks and whites collected data on numerous demographic, lifestyle, and clinical variables spanning multiple clinic visits. Unlike prior investigations, ARIC allowed for extensive adjustment of possible confounders over time, according to Dr Michos. It also contained information regarding initiation of lipid-lowering medication use during follow-up. 

Dr Michos said further research is warranted, including randomized, controlled trials, to assess whether treating vitamin D deficiency can impact lipids and thereby influence CVD risk.

References

  1. Faridi K, Zhao D, Martin SS, et al. Vitamin D and Change in Lipids Over 5 Years: The Atherosclerosis Risk in Communities (ARIC) Study. Presented at: ACC 65th Annual Scientific Session & Expo; April 2-4, 2016; Chicago, IL.
  2. Lupton JR, Faridi KF, Martin SS, et al. Deficient serum 25-hydroxyvitamin D is associated with an atherogenic lipid profile: The Very Large Database of Lipids (VLDL-3) study. J Clin Lipidol. 2016;10(1):72-81. doi:10.1016/j.jacl.2015.09.006.

More on Vitamin D…Friend or Foe?

Mushrooms are the >>>ONLY<<< vegetarian/produce based food that can make vitamin D. Actually, they contain a “pro-vitamin,” or precursor, called ergosterol that is converted into vitamin D when exposed to the sun’s ultraviolet (UV) radiation—similar to how your skin synthesizes the vitamin in response to sun exposure. -Berkeley Wellness

Ergosterol is a sterol found in cell membranes of fungi and protozoa, serving many of the same functions that cholesterol serves in animal cells. Because many fungi and protozoa cannot survive without ergosterol, the enzymes that synthesize it have become important targets for drug discovery. Ergosterol is a provitamin form of vitamin D2; exposure to ultraviolet (UV) light causes a chemical reaction that produces vitamin D2.

Ergosterol powder is an irritant to skin, eyes, and the respiratory tract. Ingestion of large amounts can cause hypercalcemia, which (if prolonged) can lead to calcium salt deposits in the soft tissues and, in particular, the kidneys. -Wikipedia

The Skin

Our body tries in many different ways to get rid of toxins. If liver, kidneys and lungs do not fulfill their tasks sufficiently, the body needs help from the skin.

The skin is the largest organ of protection and defense. It is a sensory organ. It serves for thermo regulation, secretion and excretion. The skin plays an important role in the elimination of toxins and can assist the kidneys in their work.

It evacuates the waste products that are classified as crystals. They are soluble in liquids and are evacuated in the form of sweat through the sweat glands. Crystals are the residues of the metabolism of food rich in protein, such as meat, fish, eggs, dairy products, legumes and cereals. Uric acid and urea are part of the group of crystals.

These may also result from an excess of refined sugar or very acidic food. Other types of waste products and toxins are excreted in the form of rashes. -Issels Immuno Oncology

Lipofuscin – Wikipedia

Liver Spots – Wikipedia

Vitamin D-Mediated Hypercalcemia: Mechanisms, Diagnosis, and Treatment

~Content Source-National Institutes for Health

Hypercalcemia occurs in up to 4% of the population in association with malignancy, primary hyperparathyroidism, ingestion of excessive calcium and/or vitamin D, ectopic production of 1,25-dihydroxyvitamin D [1,25(OH)2D], and impaired degradation of 1,25(OH)2D. The ingestion of excessive amounts of vitamin D3 (or vitamin D2) results in hypercalcemia and hypercalciuria due to the formation of supraphysiological amounts of 25-hydroxyvitamin D [25(OH)D] that bind to the vitamin D receptor, albeit with lower affinity than the active form of the vitamin, 1,25(OH)2D, and the formation of 5,6-trans 25(OH)D, which binds to the vitamin D receptor more tightly than 25(OH)D. In patients with granulomatous disease such as sarcoidosis or tuberculosis and tumors such as lymphomas, hypercalcemia occurs as a result of the activity of ectopic 25(OH)D-1-hydroxylase (CYP27B1) expressed in macrophages or tumor cells and the formation of excessive amounts of 1,25(OH)2D. Recent work has identified a novel cause of non-PTH-mediated hypercalcemia that occurs when the degradation of 1,25(OH)2D is impaired as a result of mutations of the 1,25(OH)2D-24-hydroxylase cytochrome P450 (CYP24A1). Patients with biallelic and, in some instances, monoallelic mutations of the CYP24A1 gene have elevated serum calcium concentrations associated with elevated serum 1,25(OH)2D, suppressed PTH concentrations, hypercalciuria, nephrocalcinosis, nephrolithiasis, and on occasion, reduced bone density. Of interest, first-time calcium renal stone formers have elevated 1,25(OH)2D and evidence of impaired 24-hydroxylase-mediated 1,25(OH)2D degradation. We will describe the biochemical processes associated with the synthesis and degradation of various vitamin D metabolites, the clinical features of the vitamin D-mediated hypercalcemia, their biochemical diagnosis, and treatment.

Vit D3 and Colorectal Cancer

~Content Source-WeeksMD

Dr. Weeks’ Comment: Inexcusably, when patients are referred or self-refer to me from nationally renown cancer  cancer centers like Mass General, Johns Hopkins, MD Anderson etc  over the past 20 years,  the oncologists there NEVER did a 25-OH D3 test.  How many peer-reviewed scientific articles at PubMed teach about the causal relationship between low vitamin D3 and Cancer?  Only 10,369!


Vitamin D Deficiency Elevates Colorectal Cancer Risk

David A. Johnson, MD

November 15, 2018

Hello. I’m Dr David Johnson, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia. Welcome back to another GI Common Concerns.

How many of you talk to your patients about vitamin D as a supplement? My message for you today is that I think we should. I certainly have changed my practice to reflect that.

We traditionally recognize vitamin D as the key vitamin for regulation of bone metabolism and homeostasis, but I want you to think out of the box here. This is incredibly important because vitamin D has a profound effect on the immune system and the intestinal barrier function. We know that vitamin D receptors regulate an active metabolite of vitamin D highly expressed in both the small and large bowel. It’s critical to regulatory actions in the gut, as it relates to proliferation and differentiation, intestinal barrier function, innate immunity, and host response. We know that vitamin D expression declines in particular as it relates to late-stage colon cancer, and it’s absent in colorectal cancer metastasis.[1,2]

Vitamin D affects the microbiome. There’s a mechanistic role in T-cell trafficking and a significant effect as it relates to the immune function. Regarding the potential for promotion of synthesis and the bad things that upregulate cancers and inflammation, we know that vitamin D actually inhibits the response of tumor necrosis factor-alpha. There’s an anti-inflammatory response with cytokine interleukin-10.[1,2]

In mouse models with vitamin D receptor overexpression, you actually can reduce the animal-related colitis.[3] If you knock out that receptor, they get spontaneous enterocolitis. If you see this knockout in humans, they really don’t respond well to any therapy other than stem cell transplant.

Vitamin D Levels and Colorectal Cancer

I wanted to share with you an article[4] that is going to be published in the Journal of National Cancer Institute in 2019, but I think it’s ready for primetime and needs to be understood now. It relates to the risk reduction for vitamin D and potential for vitamin D replacement.

This new study supports the idea that vitamin D deficiency makes a difference. Researchers pooled data from 17 study cohorts (5706 colorectal cancer patients and 7107 controls) to determine colorectal cancer risk at various ranges of vitamin D. They used the traditional measure for vitamin D deficiency of < 30 nmol/L. The threshold for sufficient bone health is around 50 to < 62.5 nmol/L. Vitamin D levels in this range were associated with a risk reduction for colorectal cancer of 19%, while those in the range of 87.5 to < 100 nmol/L were associated with a 27% risk reduction.

The results essentially show that the more vitamin D you get, the better. However, there seemed to be a plateau effect at 100 nmol/L. It didn’t mean that more was better forever; there wasn’t a linear relationship. Nonetheless, it raises the bar for vitamin D supplementation in our patients.

Putting It Into Practice

I’ve also used supplementation in patients with diverticulitis, which we know to occur more frequently in patients with lower vitamin D. When you get into some of the anti-inflammatory effects of vitamin D on proliferation, differentiation, barrier function, and immune response, it makes sense to start looking at this in inflammatory/infectious disease as well.

In summary, vitamin D is really essential in homeostasis and signaling. It affects the microbiome and has a direct effect on host intestinal inflammation. We do know that this certainly plays out in inflammatory bowel disease.[5]

It remains to be determined whether supplementation makes a big difference as far as clinical outcomes. However, to me, there’s clear evidence that it modulates inflammation, maintains epithelial integrity, and reduces intestinal proliferation. In my practice, it’s ready for primetime. I think it should be in yours as well.

Start to look at supplementation; perhaps measure the patient’s vitamin D levels, and monitor and target it in patients—particularly those at risk. I do think this represents translational, bench-to-bedside research that is ready for primetime now.

I hope this leads you in the next discussion with your patients about ways to use vitamin D beyond bone homeostasis.