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Dr Michael Osiecki



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22.01.2022 When we talk about bone health, the discussion often revolves around vitamin D and inorganic elements like calcium, magnesium and phosphorus. But bone is also composite material of protein (collagen) and the inorganic compounds give it the strength and flexibility which it requires. Unsurprisingly, protein deficiency and other wasting diseases like sarcopenia have been associated with increase risk of bone breaks and osteoporosis. So I wasn't too surprised to see this new ob...servational study on the effect of different diets on the risk of bone breaks: https://bmcmedicine.biomedcentral.com///s12916-020-01815-3. They found that people consuming vegetarian and vegan diets (even more so) had a higher risk of breaks when compared to meat or fish eaters. The risk of hip fracture was higher in fish eaters (hazard ratio 1.26; 95% CI 1.021.54), vegetarians (1.25; 1.041.50), and vegans (2.31; 1.663.22) and vegans also had a higher risk of total fractures (1.43; 1.201.70), leg fractures (2.05; 1.233.41), and other main site fractures (1.59; 1.022.50) than meat eaters. When they adjusted for variables, dietary protein and calcium had the biggest effect on risk profiles between meat and non-meat eaters. This suggests these dietary insufficiencies could be a driving factor. Although it's possible to get the required amino acids from plants, you have to be very focused in your diet to make sure you are getting them. Most vegetarians and vegans often fail to reach the required level of complete protein as well as minerals like calcium in their diet. It's also important to point out that this is more than just your essential amino acids that are lacking in these diets. Amino acids including taurine, cysteine, beta-alanine (alanine) and histidine can also be deficient. Let's take a moment to point out the importance of the essential amino acid histidine. The combination of beta-alanine and histidine make carnosine, which has so many important roles. Keep your eyes peeled for more posts on histidine because it is highly underestimated and supplementation has many clinical benefits for mental health, diabetes and obesity. So if you are treating a patient or are a vegan yourself, be sure you are getting the right amino acids and essential minerals on top of being vigilant about vitamin B12. This can't be taken lightly because the increase risk of fractures, particularly as people age, can lead to a decrease in quality of life, or in elderly people, death. Michael O



17.01.2022 When we look at the evidence, Omega-3 supplementation can appear complicated at first. The devil is in the detail and we need to look closely at the dosage, EPA/DHA composition, participant inclusion, length of the trial and the study design itself. The variance in these aspects is why we often end up with one study showing a benefit like the REDUCE-IT trial https://www.nejm.org/doi/full/10.1056/nejmoa1812792 while another study shows the opposite. This newly published study...Continue reading

16.01.2022 Type 2 diabetes is a complex disease that can be grouped into 5 subtypes, that require different treatment: https://diabetes.diabetesjournals.org/content/69/10/2086. How people get there is as important as treatment because this is what guides prevention strategies. What researchers have uncovered is that there are six prediabetic subtypes which differ in their development of the disease, diabetes risk, and the progression of secondary diseases. Just like the different subtyp...es of diabetes, these aspects also require different interventions: https://www.nature.com/articles/s41591-020-1116-9. The 6 groups can be divided into low and high diabetes risk. Cluster 1 and 2 are healthy individuals with the majority being slim with a low risk of diabetes or development of complications. Cluster 4 are overweight people but still have a healthy metabolism. Clusters 3,5 and 6 are associated with an increase risk of developing diabetes. Cluster 3 are people that produce too little insulin and therefore have a high risk of developing diabetes. Cluster 5 have pronounced fatty liver, are overweight or obese, are developing insulin resistance and therefore have a very high risk of developing type 2 diabetes. Finally, cluster 6 has renal damage already present before diabetes is diagnosed. This subtype has the highest mortality of any prediabetic subtype. I think it very interesting as the 3, 5 and 6 subtype really give you a clue on the type of prevention required. The focus would include increasing insulin production, increasing insulin sensitivity and improving the function or preventing decline in kidney function.

15.01.2022 Vitamin D has certainly been taking centre stage in COVID-19 treatment and prevention. There are many observational reports looking at populations with high serum D3 vs low serum D3 and the clinical outcomes. In terms of the evidence tree, it's nice to see some actual international clinical trials. Although in small numbers, it does add to the pool of evidence for the benefit of vitamin D3 and in this case, for the treatment and prevention of more serious illness. One study... using 60,000 IU/day of vitamin D3 showed that more patients recovered in a two week pereiod and had decreased fibrinogen levels: https://pmj.bmj.com//ea/2020/11/12/postgradmedj-2020-13906. (alternate link https://pmj.bmj.com///2020/11/12/postgradmedj-2020-139065) This indicates a decrease in clotting seen with COVID-19 patients which is a major factor of mortality or serious illness associated with this virus. Another study supplemented directly with calcifediol or 25-hydroxyvitamin D. Results did show a decreased risk of admission into ICU although they didn't observe a statistically significant decrease in the severity of the disease. Larger trials are needed to see if there is indeed an associated improvement: https://www.sciencedirect.com//artic/pii/S0960076020302764 Given that ICU bed numbers are very limited, this is still an important outcome. Many European health departments have released white papers discussing the need to make sure people have high enough vitamin D levels and to supplement if required. There has also been support for Vitamin C and Zinc in treatment and prevention of COVID-19 from these departments as well. Although we are lucky here in Australia with community transmission under control, it still important to make sure we are getting enough vitamin D. Since summer is now upon us and we are finally free to travel to the beach, I'm sure we will be getting some good doses of Vitamin D. We do, however, have to be mindful about skin cancer and those like me with sensitive skin (which can burn even on a overcast day) just have to be a bit more careful on our trips to the sandy shores. Michael



14.01.2022 Dendritic cells are responsible for the immune response in skin allergies. Interestingly, as these cells are not generally present in the dermis, up until now we have had no idea how skin contact with allergens (e.g. pollen and animal fur) results in an immune response. In a new study, researchers have identified that there are key nerve cells in the skin that are responsible for detecting allergens and activating the immune response through dendritic cells: https://www.cell....com/immuni/fulltext/S1074-7613(20)30413-1 These TRPV1+ sensory neurons are responsible for detecting allergens and activating the itch and pain sensations we experience. These cells on activation also release the neuropeptide Substance P which stimulates local dendritic cells that then migrate to lymphatic vessels to initiate T-helper-2 cell differentiation for the allergic immune response. With this research, they observed that without this sensory neuron activation of an allergen, there is no dendritic cell activation. Even when dendritic cells were exposed to the allergen in vitro, no activation was observed. This indicates that we have been targeting the wrong area for treatment of skin allergies by focusing on the immune aspect. Capsaicin can reduce Substance P: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3169333/ Phospholipids can help support the level of endocannabinoid precursors such as phosphatidylethanolamine and diacylglcerol: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC382975/ Nutrients including dl-phenylalanine increase endogenous opioids (opioid drugs do as well): https://pubmed.ncbi.nlm.nih.gov/6192685/. Finally, adenosine can help in reducing substance p levels: https://pubmed.ncbi.nlm.nih.gov/9296420/ All the above are also Nk-1 receptor blockers (the receptor that Substance P binds to) and play a role in mood disorders, IBD, nausea, rheumatoid arthritis. Michael

10.01.2022 Hyperbaric oxygen therapy is something that I'm aware of but I'm not familiar with the evidence for its health benefits. For those who haven't heard about it, it is where someone is exposed to high pressure and concentration of oxygen. Our normal atmospheric exposure is around 21% oxygen. I was interested to see this recent clinical study on the aging parameters of telomere length in immune cells and the level of cellular senescence: https://www.aging-us.com/article/202188/t...ext The intervention was quite intensive (daily sessions for 60 days) and over this time they did observe quite a significant increase in telomere length in immune cells. Depending on cell type, this increase was between 20%-37%. Researchers also noticed a 37% decrease in senescent T helper cells which is very important in maintaining immune function. Although this study had no placebo control, the fact that we see improvement after the treatment course does warrant further interest. This is especially so in relation to how the treatment decreased the number of senescent cells in the immune system. It helps me understand why some cancer practitioners use this method. I'd still like to see some better designed studies for this method before advocating such a treatment but it's definitely something to watch closely. Michael

10.01.2022 I found this great review a while back on the interactions between medicinal herbal constituents and the absorption of vitamins and minerals: https://academic.oup.com/advances/article/9/4/524S/5055954 There is actually a big knowledge gap in this area but it is important to be mindful of this potential interaction when co-prescribing both herbal and nutritional supplements. The effect of taking herbs may in fact be causing deficiencies due to a binding action on vitamin and minerals both from dietary or supplemental sources. Michael O.



07.01.2022 Food allergies are becoming increasingly common with 8% of children in the USA alone presenting with potentially lethal immune responses to foods like milk and nuts. Prevailing theories surrounding this rise in allergies includes the hygiene hypothesis. We live in a very clean environment which doesn't stimulate or train our immune systems at a early age. We need this challenge so that we respond accordingly to an immune stressor and not hyper-react to it. Furthering this,... some experts penned a perspective in Cell highlighting that hygiene through the food supply chain may also be a contributing factor along with the rise of processed foods: https://www.cell.com/cell/fulltext/S0092-8674(20)31677-9. The authors point out that we no longer see many paracites in our food and that the increase of additives and chemicals making their way into our food supply stimulate our immune system. The immune system then targets the food we eat and develops these allergies towards them. In a nutshell, these added chemicals in our foods, more so in process foods, make our immune system target food proteins and react in a way we would to toxic substances. We have to be very careful how we grow, source and prepare our foods in order prevent future generations from developing more allergies.

05.01.2022 We have seen a candidate vaccine come through with the announcement of the BioNtech developed, Pfzier produced COVID-19 vaccine early this week. While the data from this vaccine's phase II/III study is yet to be released, other than the early set of data announced in the media, I thought it would be worthwhile to provide you with some published information around mRNA vaccines and the Phase I data for this candidate vaccine. Here is a great review from 2019 on mRNA vaccines ...in infectious diseases. The mRNA basically encodes a spike protein, or any identifying part of the virus to the immune system, and uses the cell's own translation machinery to produce the protein and put into circulation for the immune system to detect. So rather than using either an inactivated viral particle or injecting the protein directly, we using our own cells to do this instead. The advantage is that it activates both the innate and adaptive immune systems rather than just the adaptive immune system which we see with traditional vaccines. https://www.frontiersin.org/articles//fimmu.2019.00594/full I think it is important to point out that mRNA vaccines for infections diseases are in early developmental stages and up until right now there are only very early, small trials on few infectious diseases. However, this technique has been used in cancer treatments for a long time which can be seen in this clinical trial from 2008: https://pubmed.ncbi.nlm.nih.gov/18481387/ This is what is commonly called immunotherapy in the cancer world which targets different immune cells. Here is a review on dendritic cell immunotherapy and the role of mRNA vaccines: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076681/ Finally, here is the phase I data for the BioNtech Pfzier vaccine where they looked at 3 dosages and two candidate designs: https://www.nejm.org/doi/full/10.1056/NEJMoa2027906 BNT162b1, encodes the SARS-CoV-2 receptorbinding domain, trimerized by the addition of a T4 fibritin foldon domain to increase its immunogenicity through multivalent display. The other candidate, BNT162b2, encodes the SARS-CoV-2 full-length spike, modified by two proline mutations to lock it in the prefusion conformation and more closely mimic the intact virus with which the elicited virus-neutralizing antibodies must interact. The dosage they are going ahead with is two doses of 30 g of BNT162b2, which according to their data in the study has marginally lesser immunological response but more importantly less adverse events. It is also important to point out that it does appear that younger patients have a stronger response and therefore more adverse events than older patients. There were no children in the data set with the youngest participant age being 18 years old. I hope this provides you with some insight and understanding so you can make an informed decision and also come up with ways of reducing risk. Michael O.

05.01.2022 We all want to eat healthier, however, we don't often think about the environmental impact of changing of people's diets, especially when we consider how much food goes to waste in the western world. https://nutritionj.biomedcentral.com//1/s12937-020-00629-6 What was interesting about this review of two studies (HEI-2015 and AHEI-2010) was that higher quality diets were associated with lower agricultural land use (think about fruit orchard vs corn field), however, there was... a higher food demand for the higher quality diet. This is due to the greater variety of fruit and vegetables included compared to highly processed diets which are made up of lots of commodity crops including corn, wheat and soy. Higher quality diets also typically increase the volume of plants consumed and this greater volume of food is required because it can be less energy dense than processed food choices. In addition, these healthier foods are not packed full of preservatives so naturally we can end up creating more waste. There was a conflicting trend in terms of the use of pesticides, water and fertilisers between the two studies due to the way it was reported. I think this brings an interesting problem to the table. We need to find a way to deal with reducing the losses due to waste in the life cycle and the potential additional resources required to maintain these higher quality agricultural products. Michael O

02.01.2022 Air pollution is one of the largest contributors to mortality in many populations around the world. Having travelled extensively through Asia, I am often affected by the poor air quality. It takes me some time to recover when I get back to Australia. I found this study useful to back up my observation that short term exposure to significant air pollution has negative effects weeks after: https://academic.oup.com/jtm/article/26/5/taz032/5486057. When we have bad pollution days or when bush fires are about, it is important to up our defences and support lung repair when exposed to these conditions. Even a small exposure has a clinically small but significant effect on our health.

01.01.2022 We generally think of dysregulation of proteostasis pathways and amyloidosis as a process happening in the brain of aging people, especially in the development of Alzheimer's disease. However, researchers have found that these proteins also aggregate in our muscles and in conjunction with mitochondrial dysfunction can cause muscle deterioration as we age: https://www.cell.com/cell-r/fulltext/S2211-1247(20)31649-1 In inclusion body myositis or other age related muscle diseas...es, the muscle cells struggle to maintain correct protein folding which leads to these misfolding proteins aggregating with the muscle. This causes both poor cell energetics (mitochondrial function) and inflammation. What was interesting is that boosting the levels of NAD+ (vitamin B3) enabled the reversal of amyloidosis and restored mitochondrial function. The mechanism by which this happens is that NAD improves the cell's natural defenses preventing misfolded proteins from aggregating which is reliant on mitochondrial energy. Vitamin B3 is so important in aging. So what form, you might ask? I really do not have a preference for which form as they all are slightly different all with benefits and pit falls. I can't confidently say which one is the best. Niacin, which some practitioners avoid because it can cause niacin flushing, is actually really beneficial because of this flush. Although you feel like you are going into anaphylaxis and covered in a giant red rash (caused by vasodilation) and difficulty breathing, research shows this is beneficial. It should also be pointed out that depending on each individual's vitamin and mineral status, I have seen flushing occur even at 20mg of niacin. So don't be surprise if you get this reaction even with a low dosage of niacin.



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