Prenatal Vitamin D and lungs (VDAART, Dr. Weiss) Interview and transcript - Feb 2026

Effects of Prenatal Vitamin D on Lung Development & Asthma YouTube, 72 minutes

Google AI Summary

(06:12) Biological Role of Vitamin D: Vitamin D serves as a "master switch" for the immune system, modulating T-cells, B-cells, and macrophages. It is particularly active on epithelial surfaces, such as the respiratory tract, where the body interacts with the environment.

(08:09) Fetal Lung Development: Research shows Vitamin D is essential for branching morphogenesis (the structural development of the lungs) and stimulates the synthesis of surfactant proteins in the fetus during the second and third trimesters. (15:49) VDAART Trial Results: The trial compared a high dose of Vitamin D (4,400 IU) against a standard dose (400 IU).[1] While initial results showed a borderline 20% reduction in asthma, 25% of the high-dose group still failed to reach the target serum level of 30 ng/mL.

(19:18) The 50% Risk Reduction: When the trial data was re-analyzed to account for the mothers' initial Vitamin D levels (level-stratified analysis), the results showed a statistically significant 50% reduction in asthma risk for the offspring.[1][2]

(21:47) Long-term Lung Function: Follow-up studies at age six demonstrated that children whose mothers maintained higher Vitamin D levels (ideally 34–71 ng/mL) during pregnancy had significantly better lung function and lower airway resistance.

(23:57) Mechanism of Action: Vitamin D reduces asthma risk by increasing sphingolipid production and lowering the incidence of preeclampsia and preterm birth. These factors collectively improve the maturity of the fetal immune system and lung structure.

(25:31) Inadequacy of Current Guidelines: Dr. Weiss argues that current recommendations from the USDA (600 IU) and the Endocrine Society (30 ng/mL) are inadequate for preventing asthma; he suggests an optimal target level of 60 ng/mL for pregnant women.

(35:06) The Obesity Factor: Because Vitamin D is fat-soluble, it is sequestered in adipose tissue. Obese pregnant women may require significantly higher daily doses—potentially 8,000 to 10,000 IU—to achieve the same protective serum levels as women with a normal BMI.

(41:39) Fetal Programming vs. Postnatal Care: Supplementation during pregnancy is critical for "programming" the fetal lung. Supplementing during breastfeeding, while beneficial, cannot fully compensate for developmental milestones missed during the in-utero period.

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Transcript

(00:03) All right, welcome everybody to today's vitamin D study hour. Hopefully everybody now is clicking in to join us. I've got Dr. Scott Weiss on today. Welcome. >> Thank you, Jen. >> All right, let's share these slides here. All right, can you see my screen? Okay, >> yes, I can. Looks good. >> Um, like I said, welcome everyone to our vitamin D study hour today.
(00:37) I'm honored to have Dr. Scott Weiss here, and he's going to be reviewing some of his latest publications on not just vitamin D, lung function, and asthma, but also on vitamin D and its distribution throughout the body and the different tissues, how the different tissues use the different metabolites of vitamin D. And it's all very interesting information that really explains a lot about especially vitamin D in pregnancy and the development of the fetus.
(01:10) Um, so like I mentioned the two publications that we have been featuring as part of the homework as well as what is going to be included in today's presentation are prenatal vitamin D supplementation to prevent childhood asthma 15-year results from the vitamin D antiatal asthma reduction trial.
(01:32) So the the vidart study and that paper was uh one of several published based on the data from that study and the other paper is vitamin D beyond the blood tissue distribution of vitamin D metabolites after supplementation published last year. So Dr. Weiss is a professor of medicine at the Harvard med medical school. He also has an extensive background in environmental health in respiratory biology, pulmonary and critical care um as well as genetics.
(02:07) So he is also the former scientific director of personalized medicine at partners healthc care system and a co-leader of the systems genetics and genom genomics unit um at the uh Channing division of network medicine at at Brigham. So he's also led or co-led a 30 investigator 110 person research group that was involved in examining the environmental exposures and genetic risk factors for the development of asthma and COPD and has led multidisciplinary cooperative studies of asthma and COPD with an international experience. He has
(02:45) authored or co-authored over 600 papers and co-written and co-edited four books including a comprehensive test textbook on respiratory genetics. And he is the recipient of several honors and awards including the American thoracic society recognition award for his scientific accomplishments. And he was also recently identified as part of the top 0.
(03:14) 004% 004% of biomed researchers in terms of the scientific impact of their work. Congratulations, Dr. Weiss. >> Thank you. >> Just a few reminders before we begin. Um, we had several questions submitted ahead of time. All other questions can be submitted to the Q&A section um and will be addressed after Dr. Weiss's presentation. Um, this will be recorded and it will be posted to our website and our YouTube at a later date.
(03:47) And as always, remember Grassroots Health as your go-to because when you measure your vitamin D levels and other health markers through Grassroots Health, you're also contributing your data to the vitamin D action study. If anybody has questions about measuring their vitamin D levels or how to optimize, which I think is probably even more important, uh you can always contact us or myself uh directly, jengrasshealth.org.
(04:14) And before we begin, um I do want to mention we're taking a short break with our vitamin D study hours for the rest of this month to focus on a few other projects. But we will be starting back up on March 4th with Dr. John White who will be talking about kind of a similar topic and we might refer to him a little bit later on um but he'll be covering his research on how vitamin D status affects the immune system.
(04:42) Um followed by uh Dr. Mace McCoy and she will be covering vitamin D and women's health on April 1st and then April 15th we will have Dr. Lelay Frame discussing her research on vitamin D exercise and outdoor activities. So once again, email us with your questions, feedback, stories, uh donations are appreciated. We are incredibly appreciative of our sponsors and our partners.
(05:10) And with that, I am going to hand it over to Dr. Weiss. Let me stop sharing for you. There we go. >> Okay. Can uh everybody see my slides? >> I can see them. Yes. >> Okay, good. Um All right. So, what we're going to do is uh uh um I'm I'm going to talk about vitamin D research before and after uh the vitamin D and asthma re uh reduction trial, the VAR trial.
(05:47) Uh um give you some background the results of Vart uh um discuss the results and try to put them in context. uh um acknowledge the people that worked on the study and then we're going to take a bunch of questions. So in in terms of background, the first thing I want you to know is is that vitamin D has profound effects on on the immune system.
(06:12) All of the immune cells of the body, T-C cells, dendritic cells, B cells, macrofasages, uh uh all of these different immune cells have the capacity to locally produce the active form uh uh of vitamin D, the 125D or calcatrial. Vitamin D also acts as a switch for the immune system to turn on and off the immune system's inflammatory response both for the innate immune system and the adaptive immune system.
(06:46) And the the VDR binding sites and and V vitamin D itself is concentrated along uh the epithelial surfaces of the body, the gut, the respiratory tract, the skin where uh uh a human the human body interacts with the environment. So that's where vitamin D is is most active. >> [clears throat] >> In terms of background, before we did the VAR trial, there were rodent studies that demonstrated a variety of different and human studies that demonstrated that vitamin D had important effects on the developing human lung. The rodent study
(07:26) showed that there were vitamin D binding sites on alvear type 2 cells that 125 uh uh um dihydroxy vitamin D stimulates surfactant phospholipid and protein synthesis. The fetal fibroblast produced 125 u dihydroxy vitamin D that the alveer macrofasages were able to hydroxilate 25D to 125 [clears throat] and in human studies uh um that vitamin D was required for branching morphagenesis in the human lung and for the development of alvear macrofasages uh in the second and third stages of uh uh fetal lung. development
(08:09) during pregnancy. Now, how common is vitamin D insufficiency and deficiency worldwide in pregnant women? That's what this slide summarizes. You can see that most of the studies have been done Canada, United States, Western Europe, uh um uh Southeast Asia, almost none at all in uh uh Africa or or uh uh um the Soviet Union.
(08:41) On the left hand side of the slide, you can see that vitamin D status is listed in varying shades of red depending on whether it's less than 12 nanogs, great less than 20 or less than 30 nanogs. And it's really those latter two categories less than 20 and less than 30 that make up the bulk of the studies. And then if we shift to the right hand side of the slide, you can see over here that serum vitamin D levels from pre that there's a wide variety between four and 60% of women have less than 20% 20 to 90% have less than 30% 30 nanogs per ml and 100% have less than 60
(09:22) nanogs per ml. So we'll come back to the 60 nanogs but the point of this slide is basically that vitamin D uh uh insufficiency and deficiency are very common in pregnant women. Third point I want to make in terms of background is just a little bit about the biochemistry of vitamin D. So [clears throat] with sun exposure uh um the skin converts uh 25 uh uh uh um uh uh uh uh cholesterol uh um to vitamin D3 which is hydroxilated first in the liver at the 25 position and then in the kidney at the one position to make the active form
(10:10) 125 dihydroxy vitamin the castle trial and that form is the form that goes intracellularly that then activates uh uh um by binding to the vitamin D receptor vacctomy. It's a downstream host of uh uh um enzymes that are involved in both endocrine and autorine and paracrine functions. Now the other important point about the biochemistry here is that the 25 OHD is what we measure uh in the serum both in pregnant women and in uh uh uh all stages of sort of clinical use of vitamin D, not the 125.
(10:53) And that's because the 125 has a very short halflife. So it's important to recognize that we're mostly interested in what's going on within the cell. We can't measure that. We don't measure the 125. We're measuring the 25. So we're measuring a proxy of a proxy to give us a sense of the vitamin D status of an individual.
(11:16) So just to summarize what was known when we started to do vart, we had identified that the vitamin D receptor locus, the gene for the vitamin D receptor was linked to asthma. We had done two studies of vitamin D intake not levels but vitamin D intake in the mother that were linked to asthma outcomes in children.
(11:44) So we found that there was about a 50% reduction in asthma in the offspring of the children uh if the mother was taking higher levels of vitamin D. Uh um so this was not a study of of levels. It was a study of uh uh uh intake. [clears throat] Clearly the endocrine effects, the bone related effects of vitamin D are linked to the serum levels of 25 OHD.
(12:14) But these immune effects that I talked about, those are really linked to the tissue levels which we can't measure. And the relationship between the serum levels and the tissue levels is not quantitatively determined. We don't really have a way of directly relating what's going on in the serum to what's going on in the tissues. And and the final point is is that there's literature about vitamin D and its effects in pregnancy that vitamin D clearly mediates a lot of different aspects of pregnancy and postnatal immune function. One way to think about
(12:47) this would be to say that the what vitamin D is doing is modulating how the mother and the fetus interact during pregnancy and controlling the mother's immune system and the development of the fetus's immune system so that the to minimize any adverse uh uh interaction between the mother and the fetus.
(13:12) So the the other point that's not shown on any of these slides but critical is is that asthma and wheezing as a as a outcome uh uh is really something that happens very early in life. Um most wheezing happens I in the first three years of life and almost all asthma is diagnosible by age five or six. So, we're [clears throat] looking at giving vi in this trial, we were looking at giving vitamin D to pregnant women to see if we could prevent asthma in their offspring.
(13:50) And here's the design of the trial. So, we enrolled [clears throat] women who either had a history of asthma themselves or having children that had asthma or had asthma and allergies in their families. And we enrolled them between the 10th and the 18th week of gestation. Uh um so their first visit, that enrollment visit was between 10 to 18 weeks of pregnancy.
(14:16) They were followed with questionnaire and blood draws. They were randomized to two groups. A group that got 4,000 IU of vitamin D plus a prenatal vitamin. So 4,400 IU in the treatment group, 400 IU in the um placebo or control group. And then monthly visits where there was a blood draw in the mother at 32 to 38 weeks. Cord blood draw uh at delivery following the pregnancy and birth outcomes.
(14:44) Questionnaires in the mother urine calcium mucratinine ratios and uh questionnaires on the blood draw in the mother at one year and the babies at one year and at three years. So the first result of the trial was how well did we do with the 4,400 IU dose to achieve 25 hydroxyd levels in the third trimester.
(15:09) So we looked at two target levels 20 nanogs and 30 nanogs both for the 400 IU dose and the 4,400 IU dose. And what [clears throat] we saw that there was a significant statistically significant increase in achieving either 20 nanogs per ml or 30 nanogs per ml with the higher dose. But the biggest point I want to make with this slide is that only 20 uh 75% of the women achieved a a level of 30 nanogs per ml uh at 32 to 30 uh 8 weeks of pregnancy.
(15:49) So 25% of the mothers were deficient in terms of our target 25 OD level that we had targeted in the trial. Then if you look at the results of the three-year study, this is a Kapla Meyer curve. The uh um proportion of free of asthma or recurrent we at age 3 years. The blue line represents the the treatment group.
(16:16) The yellow line represents the control group. And there was a reduction of 20% in the treatment group relative to the control group. But this was a borderline statistical significance. It didn't reach the stat statistically significant level of 0.05. And most importantly, it didn't approximate the 50% reduction that we saw in the observational studies.
(16:45) So why were the VAR analyses not statistically significant? Well, I already told you that we didn't give enough vitamin D. only 75% of the trial participants achieved target serum level of 30 nanogs per ml. The second thing uh uh um is that we didn't give the vitamin D early enough during pregnancy. You know we were enrolling women 12 to 18 weeks during the pregnancy but branching morphagenesis begins as early as 8 weeks in pregnancy.
(17:13) So there was a significant period of lung develop development that was going on prior uh uh uh to enrollment. And the third point and this is a particularly critical point. There was vitamin D that was present uh uh in both the treatment and the placebo arms uh at the onset of the trial. And what this meant was is that and if you looked at the levels of vitamin D on average in the treatment group and the placebo group at baseline it was about the same.
(17:44) It was close to it was 29 nanogs per ml or close to 30. But this mclassification uh uh led to reduced power to detect a difference between the treatment and the control group which is something that's unique to nutrient trials and not what you would see in a drug trial. In drug trial, you would see drug or no drug.
(18:06) In a dietary trial or a nutrient trial, you see more nutrient versus less nutrient. So, we did a a metaanalysis with the copsac study and this was published uh in this paper in plus one. uh the top uh uh meta analysis shows that when you combined our results in cops act that now we would get statistically significant uh uh results uh uh with about a 25% reduction.
(18:42) This still didn't approximate the level of the reduction that we saw in the observational studies in the lower panel. What you see is uh um a a a level stratified intent to treat analysis. So we stratified the intent to treat analysis by the baseline level uh at the start of the trial. This is still an intent to treat uh it's still the standard intent to treat analysis, but we've added this additional constraint that uh uh um we we considered the baseline level.
(19:18) And when and when we do that, the results are not only statistically significant, but they're almost exactly the same as the effects that we saw in the observational studies. We see now uh um a 50% reduction that is statistically significant. The the next thing we looked at and uh um this this has been published in this paper in biomedical pharmarmacotherapy uh um is we looked at the asthma risk of asthma as a function of the maternal vitamin D level on the lefth hand panel at 10 to 18 weeks of gestation and in the right
(19:59) hand panel at 32 to 38 weeks of gestation. And so this this blue line and the light blue confidence limits that you see on the left and the right suggests that uh uh the maximum reduction that that the reduction of risk with an increase in vitamin D level is linear. uh um a a and that the maximum reduction uh um is occurs at a serum level in the mother closer to 60 nanogs per ml rather than 20 or 30 nanogs per ml.
(20:39) So this is these figures are part of the basis for suggesting that uh uh the the level in the pregnant woman should be at 60 nanogs per ml not at 30 nanogs per ml if you want to prevent asthma wheezing in her offspring. Final [clears throat] uh uh results from the trial is we looked in a subset of the subjects at the uh effect of the maternal uh uh 25 OD level on the lung function of the children at age six.
(21:08) The left hand panel plots airway resistance where a lower amount of resistance uh um shown in blue versus the higher resistance in red or higher lung function in the right hand panel which is in FEV1 forced expiratory volume in one second. Again, blue is better, red is worse. Suggesting that those uh uh uh who had a mean gestational 25D uh uh of 34 to 71 nanogs per ml, the dark blue, had the best lung function of the children at at age six.
(21:47) So improved lung function at age six, reduced asthma at age three and age six uh um [clears throat] are what we saw uh when we did the appropriate analysis in vart. So vitamin D is necessary at every stage of pregnancy and beyond. Vitamin D sufficiency early in pregnancy has a greater effect on asthma outcomes than later in pregnancy.
(22:09) Nutrient trials are fundamentally different from standard drug trials because there's contamination in the control group. Level stratified intend to treat analysis suggest congruence between the observational and clinical trial results when initial levels of vitamin D are accounted for and the effects of vitamin D are statistically significant at 3 to 6 years uh for asthma and for lung function at age six.
(22:33) Now let's try to take these trial results and put them in some sort of context. So, the first thing I would say is is that there are variety of nutrients and I've plotted vitamin D, vitamin A, omega-3 fatty acids, and vitamin C here that have some degree of effect on airway development, lung development, immune system development uh a and are deficient during clinical uh during pregnancy and and uh have been looked at in controlled clinical trials.
(23:04) And really vitamin D only meets is the only one of these nutrients that meets all of these criteria. Uh um I I think there is some suggestive evidence that there's that omega-3 fatty acids may interact with vitamin D. uh um but but uh uh of all of these nutrients, the results are most consistent for vitamin D in terms of its overall impact and and and and the data is the strongest.
(23:36) It's important to recognize how vitamin D is actually working here. I didn't go into the genetics and genomics of this. It's it would have taken me too much time. It's a whole separate talk. But the way increased vitamin D works, it decreases preeacclampsia risk. It decreases pre-term birth risks.
(23:57) And by both of the the effect of both of those is to increase gestational age, increase the sphingo lipid levels in the lung, which improved improves immune system maturity and lung maturity and then and hence reduces childhood asthma. So we have a pretty good idea that that the primary biochemical pathway is sphingo lipids. uh uh a and that the effects of vitamin D on child asthma we is at least in part mediated by the improvements in preeacclampsia and preterm birth uh uh um a as as well as directly on uh improving gestational age. So
(24:40) preventing preterm birth and preeacclampsia with higher vitamin D coordinate maternal with the fetal innate immune system and allows the fetal adaptive immune system to develop appropriately over the first years of life. Reduces the inflammation that's seen in early pregnancy with implantation. Improves branching fetal morphagenesis and alvearization of the fetal lung preventing alvea wall remodeling.
(25:07) genetically control and directly increases sphingo lipid production, enhances the fetal response, the viral infection in early life, decreases the allergy response, increases the infant lung function. So, these are all of the different ways that vitamin D prevents asthma um in uterero and an early childhood.
(25:31) Now, what's the potential public impact? Well, Vart [clears throat] suggests a 50% reduction in asthma risk at a suboptimal dose, maybe 80 to 85% reduction at an optimal dose. We can discuss what that optimal dose is when we get to the questions. The risk of childhood asthma is a continuum. As you can see from those risk curves that I showed you, it's not categorical.
(25:53) The higher the level of vitamin D early in pregnancy, the lower the risk. Long-term protection is linked to change from baseline level with the intervention. prevention is directly linked to early intervention with preconception being best and the optimum serum level is probably 60 nanogs per ml not 30. So the magnitude of this problem if you've got 70% of pregnant women with vitamin D levels less than 30 you have almost 100% of pregnant women who have vitamin D levels less than 60.
(26:23) Current recommendations for vitamin D uh uh intake during pregnancy are all inadequate. The USDA recommends 600 IU of vitamin D, but we were using 4,000 and we didn't get a high enough dose. The IO recommends a serum level of 20 nanogram per ml during pregnancy. It's totally inadequate. The Endocrine Society recommends a serum level of 30.
(26:46) Again, with a dose up to 4,000, which is what we used, which is probably not enough. Uh the Cochran collaboration recommends further studies and their meta analyses do not account for either obesity or baseline level. Uh and most OB programs including the Brigham do not recommend vitamin D supplementation during pregnancy.
(27:07) One of the places that does is the University of South Carolina in Charleston where Bruce Hollis is and um is at. So finally uh these are all of the people that worked on the trial. Uh um Bruce was a um consultant to this study. I love people from the Channing division of network medicine who did the analyses that I presented to you.
(27:30) Uh collaboration with the people at COPSAC uh [clears throat] three clinical centers, Kaiser, Washington University and St. Lewis and uh uh um uh BEu Medical Center, my long-term colleague Gus Latanwa and the NHLBI who funded the study. So, why don't I stop there and stop sharing and uh um pretty good. We're almost at half an hour.
(28:00) >> You did fantastic. >> Uh went through a lot of material. Uh um so now uh um we we can take questions. We've got Jen Jen's got some questions that she's going to ask me that but then people uh if they have other questions they could put them in the chat. >> Yes. And and I do want to mention just a few other things before we start.
(28:23) Um, you know, we've seen evidence that if a pregnant woman uh enters pregnancy with a vitamin D level of at least 40 nanogs per milliliter, her risk of preeacclampsia is virtually none. Does your research agree with that? >> Um, I I would I would say let me just say a couple things. I I think that almost th this demonstrates how difficult it is to do nutrient trials during pregnancy because ideally if you were going to do a trial you would randomize people pre- pregnancy and so I I I think the idea that women going into
(29:09) pregnancy having a level of at least 40 even if 60 is the ideal you're less likely to have a miscarriage. You're more likely to carry a baby determ. You're less likely to have preeacclampsia. A less likely to have preterm birth. And you're going to be less likely to have a child that has asthma we in in asthma and wheezing during their first few years of life.
(29:36) So I I would say it would be ideal if every pregnant women went into pregnancy with a level of 60, but 40 is pretty good. and and and and I and I think that um the the risk of preeaccl preeacclampsia is marketkedly diminished uh uh uh w with a level of 40 uh probably not to zero though. >> Okay. All right.
(30:01) And and you know again I the importance of nutrient study design especially in terms of vitamin D when you're looking at studies that don't include pregnant women it's already difficult enough to analyze it. uh there's just so much research that's been done incorrectly, we could say, especially ignoring the baseline levels and all of that.
(30:22) But then, as you mentioned, when you start looking at pregnancy and prenatal outcomes, uh you're right, so much happens at that very beginning part of pregnancy before a woman usually even knows that she's pregnant. And um I think you and I had this conversation before. To have a very well-designed randomized control trial that enrolled women preconception would cost a ridiculous amount of money and would probably never happen.
(30:48) [laughter] >> Yeah. >> Um but but speak to the safetiness of vitamin D. Have you ever seen any issues with toxicity? And um have you ever, you know, given uh pregnant women more than 4,400 and seen any issues with toxicity? what what are your observations with that? >> Yeah, so we we monitored we one of the things that was required by uh uh um NHLBI was to do very careful safety monitoring during VR we saw no adverse side effects.
(31:22) I think I think that if you've got uh uh people who have normal renal function, you know, their kidneys are normal, um the the chances of any adverse side effects during pregnancy with with doses uh uh of 6,000 or 8,000 or even 10,000 IU a day uh are really none. Uh um I personally have not done any studies w with doses higher than 4,400 IU, but there are at least two or three studies reported in the literature in pregnant women that have used 6,000 and and and 8,000 and no adverse side effects.
(32:07) Uh um again based on our trial to get to 60 nanogs per ml in everybody would would require uh uh at least 6,000 if not 8,000 IU to to get everybody up to 60 nanogs per ml which would be what what I would view as minimal risk. So I I think for young healthy pregnant women having that s I have not seen any any side effects uh but I haven't done studies w with w with those higher doses >> although there are a few reported in the lit literature.
(32:47) >> Thank you. Okay. Um and you and I had a conversation before we started about the importance of dosing by weight or considering obesity. um as you're deciding how much to give. Uh you've seen results from trials such as your own trial and the vital trial um that have been reanalyzed based on BMI and you see the effect of vitamin D on uh intake on those health outcomes but only among those with normal BMI.
(33:23) Can you kind of go over the importance of that? What that? >> Yeah. So, so, so I think this was the hottest topic at at the vitamin D workshop in Montreal uh uh um this past year 2025. Uh um so in in the vital trial, which was looking at adults with heart disease and cancer outcomes, what they found was when they stratified by BMI and looked at normal weight individuals, what they saw was a protective effect from vitamin D that they didn't see before.
(33:57) and it was uh and and they saw no effect in the obese people. When we reanalyzed the results of Vart by the baseline pre-preg BMI, we found that there was no effect of the vitamin D on preeacclampsia and preterm birth uh uh in those mothers uh uh that that were obese uh entering Vart. Uh now vitamin D I is a fats soluble vitamin.
(34:35) So if if you for whatever level of vitamin D you're taking there's going to be sequestration of vitamin D in the fat. and how this the the uh this actually works. Again, it we don't fully understand all of the biochemistry here, but but but for any given dose of vitamin D, a chunk of that vitamin D that's ingested is going to go into the fat.
(35:06) A and the fatter you are, the more that's going to happen. So that means that less vitamin D is available for use by the immune system and use at these mucosal surfaces and so on. So what we've shown in vdart is is that if you uh uh stratify by uh uh the level of obesity that the the the the uh uh uh um you you can overcome the effect of the obesity by giving a higher dose.
(35:43) So, so if you give a higher dose in the obese, you can then prevent some of that preeacclampsia, pre-term birth, asthma we may be an additional component of the obesity because obesity is an inflammatory state where it's influencing the biochemistry of what's actually happening. with vitamin D metabolism.
(36:16) We don't know the answer to that. But but but I think the the the basic point here is that now what we're saying and I think this is going to be the consensus opinion is is that you almost have to have two sort of separate dosing standards. A set of standards for people that are have normal weight and a set of dosing standards for people that are obese.
(36:43) And so while two to,000 to 4,000 IU may be fine to prevent cancer and heart disease I in the non-obese you you might need four or six thou four to 6,000 IU of vitamin D in the obese to get the same reduction in cancer and heart disease risk. Those studies haven't been done, but it would be my intuition from what I know about how vitamin D is a fats soluble vitamin that that there's this additional a and I think I mentioned this to you before we got on the webinar is is that in some ways you can conceive of pregnancy as
(37:27) almost an obesity like state, right? because what you've got is a placenta and a fetus that need a requisite amount of vitamin D independent of of the mother. So that they're incre the reason that you need this higher dose six to 8,000 or 6 to 10,000 in the pregnant woman is is that you've got to have adequate amount available for the for the fetus.
(37:55) So if you add obesity and the mother on top of that, you're you're going to need even more. >> Mhm. [laughter] H >> I think that what again the Cochran collaboration which does all these metaanalyses and is sort of deemed the uh uh uh um arbiter of you know uh what's real in the clinical trial space. They don't consider obesity and they don't consider baseline levels.
(38:25) So in my view, most of those metaanalysis that they do don't really get at the magnitude of the problem in terms of what's actually going on. >> Right. Right. And I think Dr. Hollik in his uh vitamin D study hour that we did last mentioned that obese people likely need at least two to three times as much vitamin D as a normal uh BMI individual.
(38:49) Um, and then kind of piggybacking on what you were saying about 6,000 closer to 6,000 possibly being uh the correct dose for a and normal weight pregnant women. Um, I did have a question about breastfeeding and I also want to add a note before I ask that question because I know that doctors Hollis and Wagner have shown in their trials um on breastfeeding mother and infant pairs showing that a breastfeeding woman needs at least 6400 IU of vitamin D a day to provide her baby with that 400 IU of vitamin D in her breast milk per day.
(39:27) And so it would make sense that perhaps that 6,400 is closer to what a pregnant woman might need as well. But one of the questions that we received was if a mother who has asthma but controls it through breath work did not supplement with vitamin D during pregnancy but supplements while breastfeeding, to what extent would her baby benefit in the same way as if supplemented during pregnancy? >> Yeah. Okay.
(39:55) This is this is a great question. I I I I think [clears throat] and and this uh uh uh cuts to the heart uh um uh uh of this uh um of the fetal origins of chronic disease hypothesis. So the fetal origins of chronic disease suggests that fetal programming of the fetus during pregnancy is critical to their post-natal disease risk. And uh uh um so let me give you some concrete examples.
(40:39) You know, pregnant women that have preeacclampsia are predisposed to have babies that are more likely to have high blood pressure. Okay, that has to do at least in part with programming the fetal vascule to respond in a certain way. So the whole hypothesis behind vitart is is that we would use the vitamin D to help the development of the fetal lung during pregnancy.
(41:12) So the asthmatic pregnant woman who only gives vitamin D postnatally is abregating or limit eliminating all of those effects of the vitamin D during pregnancy. So they're they're they're going to have a baby that's got an abnormally developed fetal lung that's going to be predisposed to asthma even if they give the baby adequate vitamin D postnatally.
(41:39) Fed didn't study this. We did not do a good job of studying post-natal vitamin D. We do have information on breastfeeding. We do have information on whether the mother took vitamin D. We do have information on the mother's asthma status during pregnancy which I can talk a little bit about.
(42:04) Uh uh uh but but to assume which the the the the the questioner's question assumes that pregnancy and postnatal vitamin D supplic supplements are are equal is is a fallacy. It's not the the two stages of life, the actual pregnancy itself I is extremely important because all of the baby's own biochemistry is being set during that pregnancy and then the baby comes out into the environment and has additional setting of that biochemistry but it's on the background of whatever happened during the pregnancy. So I I I would say
(42:52) that breastfeeding pregnant women require at least 6,000 IU of vitamin D. Uh uh um you know, I would say that if the mother was getting 6,000 during pregnancy that maybe she should be taking 8,000 postnatally if she's breastfeeding. Uh, it's not clear to me that 400 IU is adequate for a neonate in the first year of life.
(43:22) I mean, I would probably lean more toward a dose in the first year of life of a thousand and then when the baby gets to be two, give it 2,000 and continue that uh uh uh on as they get older. Uh, and there's no question that during that first year of life, what the baby is doing is switching from its own innate immune system to developing its adaptive immune system and vitamin D is enhancing that immune system transition.
(44:01) So, this is a critical stage in the immune system development of the child. But I think I think it would be wrong to assume that these two stages of uh development are equal. >> Right. Right. No, the other thing beneficial to supplement during breastfeeding um as soon as possible. Uh but you're right, the programming pre-programming happens during pregnancy for the most part.
(44:29) >> The the other point that this question brings up is the uh control of the mother's asthma. We found very definitely in Vart that the better the mother's asthma was controlled during pregnancy, the better the outcome uh um of the baby. Uh uh so uh uh um asthma control during pregnancy does influence uh uh uh the fetal development.
(44:58) >> Okay. Thank you. And and there was a question submitted uh that's along the same lines. Is there any research or information on whether vitamin D helps um parents with asthma or patients with asthma? It might be typed in incorrectly, but what about later on in life? What what research have you seen uh in terms of vitamin D and and asthma? >> Yeah, so that's a that [clears throat] that's a great question.
(45:22) That's a that's a secondary prevention question. you know, how much can you improve the asthma in either children or adults uh for people that already have asthma. And I think the answer to that is that uh most savvy asthma doctors do uh uh prescribe vitamin D to uh uh their a asthma patients.
(45:53) And the reason for that is that there's immune benefit to the vitamin D because what happens with asthma is that these patients for the most part take inhaled cortosteroid and that inhaled cortosteroid is less effective. you're more likely to have steroid resistance if the vitamin D level in the asthmatic patient is low.
(46:24) So by giving vitamin D, you enhance the ability of the inhaled steroid to actually get into the airway epithelial cells and decrease inflammation. So uh uh I I would say that the secondary prevention trials have been a mixed bag for a lot of the reasons why nutrient trials are are have been a mixed bag uh uh uh for other reasons they have used too short a runin period not a high enough dose haven't adjusted for initial level all of those problems so I would say that the clinical trials data supporting my opinion is maybe less good than what I would
(47:14) actually do as a asthma specialist taking care of a patient. >> And you and I did start also talking about the certain tissues that had a um higher need or affinity for vitamin D. And I you know you mentioned it briefly in the beginning but according to your your other research paper like for example um not just asthma but let's say somebody has colon cancer and we know that research has shown a very strong correlation between colon cancer um and vitamin D levels.
(47:50) Now, could it be that it's there's certain uh tissues that require more vitamin D maybe because they express the vitamin D receptor more and in situations that are affecting those specific tissues or organs? Would that be a higher indication that vitamin D might be of higher priority for them? >> Yeah.
(48:13) So that I I think that um when you and I were going over the questions, this the person that put in this question talked about 50, you know, vitamin D being associated with protection for 50 cancers and what was the relationship of tissue specificity of vitamin D in these cancers and so on and so forth. So I first [clears throat] of all let me say I'm a genomics expert.
(48:41) I'm an asthma expert. I'm a vitamin D expert, but I'm not a cancer cancer expert. So I have not personally reviewed all of the literature about vitamin D and the 50 cancers. So I can't tell you about that. It stands to reason to me that uh uh uh um cells or tissues that express the vitamin D receptor might be that those cancers might be more or less protective.
(49:24) vitamin D have have a have a more protective effect. But as I said to you, I don't know of any so one could one could use a technique called chipsseek to tag all the vitamin D receptor binding sites in the human genome. And this study has been done by the way. So all that that the chips seek for vitamin D receptors has been vitamin D receptor binding has been done.
(49:55) But you could go look at the those tissues that are encoded by those genes and then determine how many of those tissues were indeed vitamin D responsive tissues. Now pretty clear that uh uh uh co colon cells absolutely that you know they're epithelial cells they're exposed to the environment they are likely to have a high propensity of having vitam vitamin D receptor binding sites but but I would also say that there are some tissues like lung tissue where the determinating determin determining effect of the vitamin D was on sphingo
(50:43) lipid biochemistry not vitamin D receptor binding where it was different biochemistry. So it it it isn't true that that would be the only way that vitamin D could be influencing these cancers. >> And didn't you start out your presentation saying that one of the observations that you had made before you started the VDART trial was that there was a relationship between the VDR polymorphism and asthma? >> Yes.
(51:15) >> Okay. >> Yeah. So you know in the in the case of so that is that is an interesting finding but it was also a finding that shows how complicated this is. So the number one genetic locus for asthma particularly childhood asthma is the the locus 17q1221. that locus has a VDR binding site in two genes ZBP and uh um one other gene I'm blocking the name of it but those VDR binding sites were were not in the vitamin D receptor they were in these these other two genes and these other two genes were critical
(52:13) for sphingo lipid production >> so I'm just saying that there's a lot of complicated biochemistry and a lot of different genes that are potentially involved and VDR is only one of those and only one of the things that's influenced by vitamin D. >> Right? And so a question from a participant to piggyback on that.
(52:37) How much do you think of that 25% group of women who did not achieve the level of vitamin D status was due to genetics? Uh yeah, you know, you you and I had this conversation before and uh um I'm a much bigger believer that genetics plays less of a role than dose. So I I I I think that the women f first of all remember that the target level was 30 and and I've already said that the target level of 30 was inadequate.
(53:21) It should have been 60. So uh the target level in Vart was pretty low. 25% of the women didn't get there. But I think that the majority of those women didn't get there because they started too low. They they were or or or they were obese uh um or they may not have been taking their medication. Now, compliance is a whole separate thing, but I I would put more weight on what their starting level was and whether they were obese than I would on their genetics.
(54:09) I think I think people get very fascinated by the genetics. The very, you know, as somebody who is a geneticist and has done a lot of genetics, I think it's very useful for looking at the ultimate biology and biochemistry of what's going on. But I think most of what determines people's levels is their behavior and and and you you know how overweight are they? How much time do they spend outside? How much vitamin D do they take? Do they exercise? Those things count 10 times more than the genetics in in in in my view >> and also affect the vitamin D level
(54:50) itself. And I think we're going to discuss that topic with Dr. Frame uh April 15th I believe. And then in conversation with Dr. Coinbra in Brazil who you know he focuses on autoimmune diseases especially multiple sclerosis. And he does a different you know he he uses therapeutic doses of vitamin D to treat uh a condition but even you know in his patients who can't learn to manage their stress.
(55:19) he he ca he can't always overcome that with the vitamin D or when p when patients do learn how to manage their stress he can actually lower their level of vitamin D but again he doses based on the PTH level and so that's a whole other this whole idea of vitamin D resistance and vitamin D dose response there are so many different factors that play into that but then also diet exercise um those are all key uh key lifestyle um things that we we really have to focus on as well.
(55:49) Um, I have two questions that I want to kind of follow up on this with. Um, kind of going back to your recommended levels and dosing. Um, I had somebody ask, "What are the safest highest doses of vitamin D to give during pregnancy? If a patient is severely deficient, as in 8 ngs per milliliter, what dose can be given as loading doses followed by a maintenance dose?" Yeah, I um again I don't have a lot of experience with that.
(56:23) We did have some women in the trial that were at eight and they they came up very rapidly with a 4,400 IU dose. Uh uh um I I'm not sure what I would do. Uh I think it would depend on exactly what stage of pregnancy they were at, you know, as to whether I would give a a a loading dose. Uh um so [sighs] I um I don't really have a good recommendation for that but I mean if somebody was you know below 10 and it was very early in the in the pregnancy you know you know I mean five weeks or something like that I mean giving a um a daily dose of 10,000 and a loading
(57:19) dose of 50,000 would be perfectly appropriate. >> Um but I think it's very unusual to see somebody at that stage of pregnancy, right? I mean most of the time people don't come women don't come to their obstitrician until after the eighth week. Um, so >> right, >> you know, I might still give a, you know, I mean, giving a 50,000 IU loading dose and then a dose of 8 or 10,000 IU daily, it's pretty, it' bring you up very fast.
(57:56) Uh, uh, and would have minimal if any side effects. I have a few more very interesting questions, so I'm going to keep it going past the hour. I hope that's okay with you. >> Uh, >> yeah. >> Given the market physiologic rise in 125 OD during pregnancy without hypercalcemia, should clinicians be less concerned about higher vitamin D intakes in pregnancy when calcium and renal function are normal? >> Yeah, I mean, I think the answer to that is obviously yes.
(58:34) I mean I think that um I think calcium has almost nothing to do with the rise in the 125 dihydroxy vitamin D during pregnancy. That that is all about providing adequate vitamin D to the placenta and the fetus >> and that's the only time in the life cycle that happens. Right. >> That's correct. >> Yeah. Yeah. Okay.
(59:00) And then one other question on the dosing questions. So, um she asked if you would normally start with 4,000 IU and then correct the dose by measuring the blood level. But, um the other part of her question, which I think is a really great question, is do you wait 2 to 3 months uh to re-measure as you know that's what we suggest you give the vitamin D level time to adjust to the dose.
(59:27) um or would you want to remeasure sooner to make sure that she's responding to that dose? >> Well, I mean, I think we have to distinguish here between she's talking about a normal adult, not a pregnant woman. >> Um, no, I think the pregnant women uh because we were discussing pregnancy. Well, you got so you you have so little time during pregnancy to I mean pregnancy happens it may seem like an eternity to a pregnant woman but it it's really it's it's over before it starts.
(1:00:10) So I I I I think based on you know what I know I what I know right now you know in terms I would give obese pregnant women 8 to 10,000 IU. I would give a pregnant woman 6,000 IU. And I would just count I I wouldn't worry too much about, you know, reme-measuring the dose. By the time we did the second dose, it was the 32nd to the 38th week.
(1:00:41) You know, the pregnancy was virtually over. >> So I I I would count on the fact that I have a pretty good idea based on the trial what sort of dosing I need to give to somebody who's obese and somebody who's non-obese and go with that. And and what percent of women were obese in the the dart trial? >> Um I think I think about half of them were overweight.
(1:01:10) >> Okay. >> Overweight or obese? Yeah. >> Okay. Yeah. So, um, I I was very honored to be a part of the Medical University of South Carolina prenatal project that Grassroots Health did along with Bruce Hollis and Carol Wagner and several other uh, key figures there. And I know that what we did, we measured at the very first prenatal appointment, measured again, I think it was around 24 to 26 weeks and then again around 34 to 36 weeks to ensure that we were dosing correctly.
(1:01:46) And we were dosing using our calculator that goes by weight, >> right? >> Um, and we continued to reme-measure the vitamin D level until that woman reached a level of at least 40. Uh so that is one way to >> that that's a perfectly reasonable approach to this. >> I don't think there is sort of one >> one way to do this.
(1:02:09) I mean you and I did have the discussion about uh uh um you know there's a lot of controversy now for non-pregant people about when uh uh vitamin D levels should should be measured or shouldn't be measured. And you know, there was just an article in the New England Journal of Medicine suggesting that primary care physicians should not measure vitamin D levels.
(1:02:34) My own personal feeling about this is that uh I [clears throat] I think that given that the health consequences of low vitamin D are so significant, I would prefer to know that my serum level is normal and I would prefer my primary care physician to measure it >> rather than not measure it. uh if there was any question about whether I was sufficient or not >> and I can't tell you the number of people in my own laboratory who didn't know they were vitamin D deficient and then they had their vitamin D measured and they were so it's it's a much bigger
(1:03:15) problem than people think particularly if you think that given this obesity thing and the fact that the level that's protective is probably for for uh uh cancer and heart disease and whatnot is likely higher than it is anticipated. You know that people keep saying oh 30 is the is the level you should have.
(1:03:45) No, I think >> in pregnancy it should be at least 60, and I'm not sure that for non-pregnant conditions it shouldn't be 60. >> Right. Right. And I think you pretty much answered this question uh with that. I'll reread it and then you can add to it if you like. Uh, what's your opinion of the Endocrine Society's decision to recommend that clinicians not test patients for vitamin D and not recommend supplements? What's the policy among the American College of Obstitricians and Gynecologists about supplementation and testing for vitamin
(1:04:14) D status? >> Yeah, I think that I think that both of both the endocrine societies recommend the American College of Obstetrics and Gynecology has no position on this. They don't have a position and I I think that uh uh the endocrine society is wrong. I mean they're they're they're basically wrong about this.
(1:04:34) I think that part of the pro I mean I mean if you talk to any of the sort of older school vitamin D expert experts Bruce Hollisuh Bruce uh Mike Hollik uh uh uh and you ask them what's your vitamin D level they'll all say 60 nanogs per ml that's what they'll say. So, I think that tells me that they know something that, you know, the rest of us ought to be listening to.
(1:05:07) >> Um, so I I I I I think that we've still got a long way to go be I think that again part of the problem here is what the geneticists call pleotropy. You've got large portion of the scientific community that sort of looks at vitamin D only in the context of calcium and bone health. And then there's a smaller more advanced group that sort of looks at this in the context of immune health, cancer, autoimmunity, and so on and so forth.
(1:05:44) And if you look at that group, that's where this higher level, the push for the higher levels is coming from. >> Right. Right. Yeah. There's certainly people who still focus so much on bone health and and that's all that matters for vitamin D and the guidelines. And um we've had Dr. uh Bill Grant and Dr. Michael Hollik and uh Bruce Hollis and several other people come out and and speak to that topic.
(1:06:16) Um and it it relates to this very last question that I have for you uh from one of our attendees. In your opinion, what differences in further research need to be looked at or threshold for total evidence needs to be reached in order to support a revision in the public recommendations for vitamin D supplementation during pregnancy? >> Yeah, great qu great question.
(1:06:38) I uh uh um yeah, you know, uh um yeah, you know, you know, they're they're going to have a consensus conference uh um that's sort of planned by the NIH for this next year. Uh it'll be interesting to see what comes out of that. Um I'm not sure that in in terms of pregnancy recommendations more clinical trials in the context of the United States are even pos ethically possible uh given the limitations on the clinical trial methodology.
(1:07:23) I think that more research clearly needs to be done on this obesity thing because if it turns out you need one sort of dosing schedule for the non-obese and another dosing schedule for the obese, [clears throat] we need to know that. Uh so I think that's probably the most important and that involves some reanalysis of the ex existing uh trial data.
(1:07:55) Uh um but I think we're a ways away from a consensus here and and it's not entirely clear to me how we're going to get to one. We're clearly going to need more research, but uh exactly what sort of research we need. It's hard to know because I think there a lot of people that don't I I I was impressed by some of the naive amongst a lot of the participants at the vitamin D workshop in in in Montreal that people who were supposed experts who really didn't understand this.
(1:08:27) So >> yeah, >> we'll we'll we'll have to see what uh it's it's clearly complicated. >> Yeah. And yet it's been um discussed far back. You Dr. Robert Haney, he published his paper on uh guidelines for proper nutrient studies including vitamin D. I think it was in 2014. We we've been talking about this for years.
(1:08:50) I had you on for a presentation where we really discussed this topic in a lot of detail. Um and I think that was well that was sometime last year of course, but it's on our YouTube. Um, so I would highly suggest that anybody who's interested in that uh go to the grassroots health uh vitamin D action YouTube channel and find our last presentation with Dr.
(1:09:12) Weiss. Um, but yeah, it's there's slow movement. You know, we went to DC uh in September and uh had our you know research and our our maternal vitamin D initiative and had a lot of great conversations. But um as somebody within all of that quoted every everything at that level moves at glacial speed up to us to >> I think I think one of the things that's most distressing to me is is that I don't think the clinical trials community has understands what Bob Haney was talking about and and to insist on uh uh uh standard clinical trials as
(1:09:57) being the end all beall particularly when you're talking about a nutrient and its actions during pregnancy. I I think you're not going to be able to achieve uh uh uh that using sort of the standard clinical trial approach. >> Right. No, not at all. And and again, you know, we've got so many great resources.
(1:10:24) Uh I did recently post one of Dr. Haney's last uh presentations that he did with us on nutrient trial design. That's also on our YouTube. I've written several blogs have a great uh download in uh downloadable infographic that reviews each of those criteria for how to review and look at vitamin D research and their conclusions.
(1:10:46) Really important to know. Um so with that, I'm going to start our closing. Do you have any other key points? Anything else you'd like to say? >> No, I think the questions were great and uh it's very good discussion. >> Thank you. Yeah, and I apologize. I did not get to all of the presubmitted questions.
(1:11:05) We went through all of the questions submitted today. Um if anybody has any additional questions, something that they're dying to get answered, please email me, Jen at Grassroots Health, and I will forward them on to Dr. Weiss. In the meantime, thank you so much for joining us, Dr. Weiss. It was a pleasure. Yeah. Thank you, Jen. >> You're welcome.
(1:11:26) Well, enjoy the rest of your day. Thank you. >> You, too. Bye. >> Bye. [music] [music]"