There was an inverse association between UVB irradiance and case-fatality rate of influenza and rate of pneumonia as a complication of influenza in the US. Both UVB indices gave similar results. According to data in Britten,24 the 1918 influenza pandemic reached eastern US cities in September, and San Francisco in October. Peak mortality rates extended from late October to early December. Based on serum 25(OH)D measurements of 45-year old British adults, levels would be intermediate between summer and wintertime values. There is other evidence for a role of vitamin D reducing the risk of pneumonia. For example, pneumonia deaths in England and Wales in the period 1988–92 had a peak-trough ratio of 2.7 with the peak in December and January and trough in July–September.31 In Ethiopia, there was a 13-fold higher prevalence of rickets among children with pneumonia than among controls [odds ratio: 13.37 (95% CI 8.08–24.22), p < 0.001] in Ethiopia.32 Low serum 25(OH)D (<22.5 nmol/L) was associated with higher risk of lower respiratory tract infection (odds ratio: 0.09; 95% CI 0.03–0.24; p < 0.001) in India.33 From inspection of the incidence and mortality rates from the 1918–1919 influenza pandemic at the total population level, it is not possible to draw conclusions about vitamin D with respect to pandemic influenza incidence. As discussed above, the established role of vitamin D in upregulating production of catheliciden, an endogenous anti-bacterial peptide, may be a potential explanation of the association we observed. An additional potential mechanism may be the role of vitamin D in the reduction of pro-inflammatory cytokines. One of the important observations of deaths during the 1918–19 influenza pandemic was that the death rate was high for young adults.34 This is different than for seasonal influenza, during which mortality rates are higher for the elderly and infants. The reason for this difference seems to be that those in their 20s and 30s have a more robust immune system which can mount a stronger attack on microbial infections. From recent studies, it has been determined that both H1N1 and H5N1 viruses induce a T-helper 1 (Th1) type cytokine response to viral infection of macrophages.35 These cytokines are proinflammatory and include IL-6 and TNFα.35 Nuclear factor kappaB (NFκB) is also an important risk factor.36 Influenza A (H5N1) viruses induce production of proinflammatory cytokines at a greater rate than do H1N1 viruses.37,38 1,25-dihydroxyvitamin D [1,25(OH)2D] reduces the production of Th1 cells, thus shifting the Th1/Th2 balance towards Th2, which is less inflammatory.39–41 1,25(OH)D has also been found to reduce the production of NFκB42 and TNFα.43 Infection of macrophages also induces a toll like receptor induction of human cathelicidin, LL-37,44 which is effective in combating bacterial infections such tuberculosis44 and others.45 Thus, an additional mechanism whereby vitamin D could reduce the severity and likeliness of death from H1N1 and H5N1 viral infections is reduced production of proinflammatory cytokines and NFκB. However, suppressing proinflammatory cytokines did not reduce the risk of death for mice infected with H5N1 viruses.46,47 These results may not apply to the H1N1 virus in humans because mice have different immune responses than humans. The possible roles of solar ultraviolet-B radiation and vitamin D in reducing case-fatality rates from the 1918-1919 influenza pandemic in the United States William B Grant et al. Dermatoendocrinol. 2009 Jul. Authors William B Grant @wbgrant2, Edward Giovannucci.

The possible roles of solar ultraviolet-B radiation and vitamin D in reducing case-fatality rates from the 1918-1919 influenza pandemic in the United States William B Grant et al. Dermatoendocrinol. 2009 Jul. Authors William B Grant @wbgrant2, Edward Giovannucci Abstract Deaths during the 1918-1919 influenza pandemic have been linked to both the influenza virus and secondary bacterial lung infections. Case fatality rates and percentage of influenza cases complicated by pneumonia were available from survey data for twelve United States locations in the 1918-1919 pandemic. This study analyzes case fatality rates and cases complicated by pneumonia with respect to estimated summertime and wintertime solar ultraviolet-B (UVB) doses as indicators of population mean vitamin D status. Substantial correlations were found for associations of July UVB dose with case fatality rates (r = -0.72, p = 0.009) and rates of pneumonia as a complication of influenza (r = -0.77, p = 0.005). Similar results were found for wintertime UVB. Vitamin D upregulates production of human cathelicidin, LL-37, which has both antimicrobial and antiendotoxin activities. Vitamin D also reduces the production of proinflammatory cytokines, which could also explain some of the benefit of vitamin D since H1N1 infection gives rise to a cytokine storm. The potential role of vitamin D status in reducing secondary bacterial infections and loss of life in pandemic influence requires further evaluation. Keywords: H1N1 influenza; bacterial pneumonia; cathelicidin; cytokines; pandemic influenza; ultraviolet-B; vitamin D.

The possible roles of solar ultraviolet-B radiation and vitamin D in reducing case-fatality rates from the 1918-1919 influenza pandemic in the United States William B Grant et al. Dermatoendocrinol. 2009 Jul. Authors William B Grant @wbgrant2, Edward Giovannucci Introduction In the twentieth century, there were three influenza pandemics, in 1918, 1957 and 1968, caused by H1N1 (Spanish flu), H2N2 (Asian flu) and H3N2 (Hong Kong flu), respectively.1 The 1918–1919 pandemic was different from the subsequent ones as it was the only one caused by an H1N1 virus, and is the only one considered in this work. “In 1918, there was one distinct peak of excess death in young adults aged between 20 and 40 years old; leukopenia and hemorrhage were prominent features. Acute pulmonary edema and hemorrhagic pneumonia contributed to rapidly lethal outcome in young adults. Autopsies disclosed multiple-organ involvement, including pericarditis, myocarditis, hepatitis and splenomegaly. These findings are, in part, consistent with clinical manifestations of human infection with avian influenza A H5N1 virus, in which reactive hemophagocytic syndrome was a characteristic pathologic finding that accounted for pancytopenia, abnormal liver function and multiple organ failure.”1 The influenza pandemic of 1918–1919 claimed many lives. While the influenza virus played an important role, there is evidence that the primary influenza infection was not necessarily the proximate cause of death. For example, the median time to death was 7–10 days, and a substantial proportion of deaths occurred greater than 2 weeks after onset of the initial symptoms.2 The delay in death has been attributed to the influenza infection allowing bacteria to colonize the lower respiratory system and produce lethal pneumonias.2,3 Bacterial pneumonia also was noted as a serious complication of influenza during 1957–8 influenza pandemic,4 and antibacterial approaches have previously been proposed for reduction of the case-fatality rate during influenza pandemics.5,6 Vaccines are the first line of defence against epidemic influenza. However, successful treatment or prophylaxis of complicating bacterial pneumonias may be important, since a presently unknown or poorly characterized virus might cause a pandemic before an effective vaccine becomes universal.2,5,6 Several months to a year are typically needed to develop and universally administer an effective vaccine for a new strain of influenza.7 While vaccines are absolutely essential for control of influenza, they are not always effective in eliminating influenza cases, and the associated risk of secondary respiratory infections, especially among older adults. It has been estimated that a recent influenza vaccine produced only a 27% reduction in hospital admissions for acute respiratory infections, such as pneumonia.8 Other epidemiological approaches, such as limiting travel and case containment, could be part of an overall plan to limit the intensity of an influenza pandemic.9 However such concepts are rarely implemented successfully. Targeted layered containment has also been proposed for limiting pandemic influenza cases in the US.10 Such epidemiological measures would have serious economic impacts. Since the fatal complications of influenza are due in part to secondary bacterial infection,2–4 the degree of immunity to the most common bacterial agents of pneumonia may be important. Exposure to solar ultraviolet-B (UVB) starts a multi-step process, starting with biosynthesis of vitamin D and its metabolites, followed by upregulation of human cathelicidin (LL-37), by 1,25-dihydroxyvitamin D.11 There are several recent reviews of the effects of cathelicidin against bacterial infections such as Mycobacterium tuberculosis.11–16 Cathelicidin appears to be effective in fighting septicaemia, in part due to its antiendotoxin effects.

Did you know Vitamin D is linked to over 200 health outcomes? A recent review highlights the risks of Vitamin D deficiency, including autoimmune diseases, cancer, and even COVID-19 severity. 📉 One groundbreaking study, “Vitamin D regulates microbiome-dependent cancer immunity,” was published in Science—a must-read for anyone interested in the future of cancer research! 🔬 Big thanks to @Dr.Grant for always staying on top of these crucial studies! 🙌 Check out more top publications of 2024 here: #VitaminD #HealthResearch #CancerImmunity #Publications2024 #VitaminDDeficiency #Wellness

Prevention and Treatment Here are representative papers published in 2024 regarding the effect of serum 25(OH)D concentrations on health outcomes. Cancer. Perhaps the most important vitamin D-cancer article in a couple of years: “Vitamin D regulates microbiome-dependent cancer immunity” published in Science [17]. It first described mouse model studies of vitamin D and cancer. In mice, higher vitamin D status resulted in greater immune-dependent resistance to transplantable cancers and augmented responses to checkpoint blockade immunotherapies. This resistance is attributable to the activity of vitamin D on intestinal epithelial cells, which alters microbiome composition in favor of Bacteroides fragilis, which positively regulates cancer immunity. Studies involving Danish cancer patients, those with the highest vitamin D-vitamin D receptor (VDR) signature levels had significantly survival rates than those with the lowest levels over 33 years for skin cancer, 12 years for sarcoma, and 10 years for liver hepatocellular cancer. This study strengthens the case for an important role of vitamin D in reducing risk of cancer. Cancer. A bibliometric analysis of global research on vitamins and cancer between 2003 and 2022 found vitamin D to be the most important vitamin for cancer prevention [18]. As shown in Table 5 in that review, nine of the ten most cited papers were for vitamin D. Colorectal cancer. A review of the benefits of vitamin D for colorectal cancer was published [19]. Figure 2 in it shows the mechanisms related to proliferation, epithelial differentiation, cell death, WNG/β-catenin signaling, immunomodulation, angiogenesis, microbiome, detoxification, fibroblasts, and stem cells. Colorectal cancer. A systematic review regarding metastatic colorectal cancer that low 25(OH)D concentrations were significantly correlated with increased risk of progression and death [20]. COVID-19. A systematic review found vitamin D supplementation had a significant beneficial effect on prevention of incidence in both RCTs and observational studies as well as admission to the ICU in observational studies [21]. In a subsequent systematic review, reduced risk of intubation in RCTs and mortality rates in observational studies were also found [22]. Diabetes mellitus type 1. An intervention study was conducted in Iran with 90 type 1 diabetes mellitus patients aged 5‒18 years [23]. At baseline, 59% had 25(OH)D concentrations below 20 ng/mL and 41% had concentrations between 20 and 30 ng/mL. Those with 25(OH)D concentration below 30 ng/mL were supplemented with vitamin D according to the 2011 Endocrine Society Guideline [8], then 1000 IU/day after achieving 30 ng/mL. After six months, 50% had concentrations between 30 and 50 ng/mL and 36% had >50 ng/mL. Levels of HbA1c declined to <8% for 10% of those with concentration between 30‒50 ng/mL, but to 69% for those with concentrations>50 ng/mL (p <0.01). Dyslipidemia. A narrative review found “on the one hand, numerous observational studies suggest a link between higher serum 25(OH)D concentrations and a beneficial lipid profile, while on the other hand, interventional studies do not demonstrate a significant effect.” [24]. Fatigue. A narrative review outlined the role of vitamin D on fatigue mitigation [25]. The effects include some related to oxidative stress and inflammatory cytokines. Some control over the neurotransmitters dopamine and serotonin have also been found. Fibromyalgia. A cross-sectional study was conducted in Turkey involving 180 female fibromyalgia patients [26]. Sixty-five percent had baseline 25(OH)D concentrations below 20 ng/mL. They were given 50,000 IU/week for 12 weeks. As a result, Visual Analogue Scale scores decreased from 7.7±1.2 to 5.1±1.2 (p <0.01) and the Fibromyalgia Impact Questionnaire score decreased from 67±10 to 54±9 (p <0.05). Parkinson’s disease. A review pointed out that vitamin D plays a role in the management of Parkinson’s disease.....

Key Points Vitamin D is arguably the most important nutrient for health and has been linked to over 200 health outcomes One review published in 2024 states that vitamin D deficiency [25(OH)D <20 ng/mL (50 nmol/L)] increases risk of autoimmune and infectious diseases, cardio-respiratory diseases, impaired muscle function and strength, diabetes, cancer incidence and mortality, and acute COVID-19 severity and long COVID risk Perhaps the most important vitamin D-cancer article in a couple of years was “Vitamin D regulates microbiome-dependent cancer immunity” published in Science; read on for more of the top papers published in 2024.

Meat is a risk factor for Alzheimer’s Disease First study to show that was a Seventh Day Adventist study in 1993 The meat eaters had Alzheimer’s Disease at 2 -3 times the non meat eaters. WB. Grant, PhD @wbgrant2 did a study in 2016 looking prevalence of Alzheimer’s in 10 – 11 countries. The total meat + eggs+ fish had the highest correlation with Alzheimer’s Disease Cholesterol is a risk for Alzheimer’s disease Trace minerals iron in meat He had studied the effect of acid rain on forest soils Acid rain leeches out the base minerals such as calcium and potassium As the pH lowers it dissolves aluminum and all the transitional ions such as iron, mercury and zinc The trees use whatever is available and can decline At the University of Kentucky, the studied the brains of people with Alzheimer’s and found exactly the same chemistry Eating animal products will increase these transitional metal ions such as aluminum or iron and reduce the concentration of calcium, potassium and aluminum Vegetables have a lot of antioxidants Some say the Mediterranean diet decreases the risk of Alzheimer’s by 50 % Of the rates of the US, Brazil or Mongolia (where there are the highest rates ) But these have twice the rate of places that have primarily vegetarian diets European Newspapers published about hamburger’s risk for Alzheimer’s Disease where as the Indian newspapers said that their diet reduces Alzheimer’s Disease His study controlled for dietary factors that meat eaters might eat fewer vegetables It is a trade off between legumes, beans rains and animal products In the tropics people eat manly legumes In the North people eat more animal products so there are latitude variations in cancer and Alzheimer’s Disease which he relates to diet The vitamin D levels average about 22 through out the world except in the Middle Easter countries where they wear a lot of clothes and don’t like to be outside during the summer.

Embrace the Sun: Are You Dying in the Dark? William B Grant, PhD @wbgrant2 Observational studies show the higher levels of vitamin D result in lower risk of cardiac diseases all cause mortality rates Swedish study, designed to study the incidence of melanoma and time in the sun, those who spent the most time in the sun had half the mortality rate after the age of 70 of those who spent very little time in the sun Melanoma No increased risks The Garlands found that Navy men submariners had more risk than those who worked on deck 5 % of all cancer cases are related to melanoma. Only 1.5 % of all cancer deaths are linked to melanoma Only 1 /300 deaths in the US are related to melanoma Sun exposure protects from melanoma by thickening the skin, tanning , producing vitamin D which does reduce melanoma Most melanomas are found on parts of the body not exposed to the sun Highest risk is for people who occasionally get sunburned. Sunscreens prevent this protection Garlands found that those in the North of 40 degrees who used sunscreen had a higher risk for melanoma. Sunscreen protected people South of the forty degrees Sunscreen does not prevent against the long wave UVA which penetrates deeper into the skin and is a risk factor for melanoma UVB and short UVA waves cause the sun-burning Wearing sunscreen every day, he believes is misguided. Sunscreen is OK if a person who rarely goes out and gets sunburned – he recommends that they put it on after a time in the sun. The following diseases are associated with lack of sun exposure Colon cancer Breast cancer New study shows that people who got their vitamin D up to 70 have 1/5 mortality than those with a serum level of 15 Pancreatic cancer Ovarian cancer Endometrial cancer Bladder cancer Brain cancer Esophageal cancer Gall bladder cancer Renal cancer Leukemia Multiple myeloma Pharyngeal cancer Prostate cancer Thyroid cancer Lung cancer Sunshine helps some of the mechanisms that cure cancer.