My experience has been mostly with higher doses of Vitamin D. Specifically answering the Multiple Sclerosis question, it was around 2002 when we started prescribing 10.000 units of Vitamin D daily to patients with multiple sclerosis due to literature data that had already been available, showing that Vitamin D is an immune-regulator, regulating the autoimmune system, and not suppressing it, stimulating the autoimmune system and efficiently helping it fight against infections, inhibiting incorrect autoimmune reactions, technically known as TH17. So Vitamin D is theoretically an ideal pharma component or substance as it offers the strength of a hormone that fights infectious diseases, since we do not trigger any autoimmune suppression, and actually the other way around, we increase the potentiality of the normal immune reactions. We started treating with 10.000 units of vitamin D daily and observed improvements in our patients. With 10.000 units the disease did not enter in remission. Relapses became less frequent but the disorder was still active. Each time our patients had emotional stress, there was still a risk, that this emotional stress triggered a new relapse. As the years went by, we were monitoring these patients with a higher dose intake and observed that, as we increased the doses, our patients had more positive effects. Approximately 2-3 years ago, we reached the ideal dosage that would suppress autoimmune disorders activities, and this is around 1.000 units per kg (body weight), daily.This dose is an average for patients, as in the reality there is an individual calculation, which could be higher or lower according to each patient’s condition. We adjust these individual doses according to the parathormone (PTH) level. As the level of vitamin D increases, the PTH level gets lower, so we try to keep the PTH level around the lower limit of the normal range. and we noticed that by keeping the PTH level around the lower limit of the normal range (without suppressing it) we may keep the disorder in remission. To reach such lower levels it was necessary to reach, in average, a dosage of 1.000 units per day, per Kg (body weight). In order to prevent side effects that can occur with these higher doses, if a cautioned diet is not followed, we excluded food products that are rich in calcium, basically milk and its sub products, and calcium fortified products, such as oat milk, rice milk and soy milk. Once this precaution is taken, a higher dose along with plenty of hydration is considered quite safe. In other words, we ask our patients to have a minimum daily liquid intake of 2.5 liters (water, juices, soft drinks, tea, soup…) all together there must be a minimum of 2.5 liters daily because then it is possible to have the diuresis of approximately 2 liters, which keeps calcium diluted and eliminated through the urine. Once calcium is diluted, i.e. avoiding calcium concentration, we can prevent the most feared manifestation of vitamin D intoxication, which is the nephrocalcinosis, The vitamin D doses (and serum levels) were progressively increased along the years. There was a time in the past when we did not have any particular diet, and we observed that the calcium levels were above normal range, so we kept the vitamin D level, but asked our patient to exclude dairy products and other products enriched with calcium. With this measure in place, we noticed a calcium level reduction in the urine, even lower than before the patient had started the vitamin D treatment. Based on that, we were able to increase vitamin D doses, and as I said, in average, a daily dose of 1.000 units per kg (body weight). For obese patients, the dose can be even higher than this average. So for example, it would not be absurd that we have a person that weights 130 kg taking a dose of 200.000 units per day. ln order to compensate the subcutaneous fat absorption, as explained by Dr. Holick, subcutaneous fat removes vitamin D from blood circulation, it is necessary to prescribe an extra amount to stop it from robbing vitamin D from subcutaneous tissue, in relation to the vitamin D available in the body. However such doses must to be prescribed under rigid clinical and laboratory control, and patients need to be seen periodically in order to check if they are following the diet, because this is extremely important. Higher vitamin D doses to these which we have been prescribing, can bring the opposite effect to the normal biological action. A person with 70 Kg that daily takes doses higher than 150.000 units of vitamin D, in any of its prescription forms, can contribute to calcium reduction from bones, causing hypercalcaemia through this mechanism. This can be blocked by administering medicines known as bisphosphonates, such as alendronate, etidronate, and others and effectively block this toxic effect. But rarely we reach these doses, just in cases of patients whose weight are well above the norm, with body mass above normal. I am not sure if I answered well about my experience with vitamin D, but I just wanted to add that, since 2002/2003 when we started, until now, we have treated nearly 1,130 patients and 70% of this number have been treated with higher doses of vitamin D. Since when we started treating patients with 10.000 units, there have been nearly 1.130 patients and the result is simply fantastic. We have some patients that are here in the audience, and we have great satisfaction in giving them a normal life back. They no longer have relapses, nor lesions in their MRI images. They no longer expect to be blind or paraplegic, or to become disabled, they simply can see a normal future in their lives. The only thing that we don’t know yet is for how long they will have to keep these higher doses of vitamin D. This is a question still to be answered. Is it associated with any other drugs? No, absolutely nothing! Just high doses of vitamin D. About the dosage form, as I said, Professor Michael Holick has given a good explanation, that there are many dosage forms that are equally effective. Whenever we use higher doses, such as these ones that I mentioned, we have observed that administering vitamin D under the tongue is a bad and ineffective form. We did not achieve the same results, and we have the impression that the lipid-based vehicle mixed in oil, produce a better effect. This is not something that has been completely documented, but the impression is that mixing it with oil brings better effects, than mixing vitamin D with any other form, even when oil is mixed with those made in dry capsules. About the use of vitamin D for patients with Parkinson: Vitamin D brings trophic effects in the nervous system, so that is very important, it also has antioxidant effects, stimulating nerve cells to produce and synthetize glutathione, which is an important antioxidant. It also produces neurotrophic factors, which are substances that keep nerve cells alive. These neurotrophic factors or neurotrophins, are produced from the glial cells, such as astrocytes, under vitamin D stimulation. Vitamin D is captured from the circulation and transformed into its active form, within the hemato-encephalic barrier, acting on all cells from the nervous system, acting on the glial cells, stimulating glial cells to produce neurotrophic factors that keep, as it is own name says, vitality of nerve cells – keeping them alive. So for any type of neurodegenerative disorder, it is highly advisable that normal levels of vitamin D are prescribed, and I think it is no use to prescribe patients with doses any lower than 10.000 units, Normally for us that depends on the patient’s weight, but for people with 50-55 Kg we prescribe 10.000 units What we do for these patients with Parkinson disorder however is only to normalize their levels, reducing the PTH that is above normal,leaving the PTH at its lower normal range. This can vary from 10.000 to 25.000 units per day for patients with Parkinson disorder, Changing a bit the theme about vitamin D and MS, for Parkison disorder it is important to note that I have seen and monitored over 1.200 patients with Parkinson disorder, The biggest problem with these patients is that the cause of the disorder seems to be a state of chronic suffering. Parkinson patients were always anxious, worried individuals that were chronically suffering. Before their diagnosis, or before the beginning of the Parkinson disorder, these individuals went through an exceptional period of emotional stress, Individuals that look at a small problem reach suffering levels beyond normal it is incredible. And this cannot be perceived if you do not interview the patient and ask these individuals specifically about this problem. Apparently, this emotional stress triggers the formation of a neurotoxic substance called salsolinol in these patients. Or its complete name, N-Methyl(R)-Salsolinol, which is a powerful neurotoxin, that destroys neurons responsible for the production of dopamine as it is formed inside the cells that produce dopamine. This substance is found in a large amount at the cerebrospinal fluid in these individuals. Patient’s deficiency of vitamin D can be corrected and it is a factor that can help these individuals, but their biggest challenge is to reach a lower level of suffering. Thank you!
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