Controversies on Vitamin K with Cristiana Paul: Rational Wellness Podcast 290
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Cristiana Paul discusses Controversies on Vitamin K with Dr. Ben Weitz.
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4:44 Cristiana Paul has been digging into the research on vitamin K since 2010 when we first learned of the effects of vitamin K beyond clotting. The three forms of vitamin K that are on the market are K1 and two forms of K2–MK4 and MK7, which is a patented form that is claimed to be more effective. But the Japanese have been doing a lot of research on MK4 for at least 30 years and found that it is very effective for osteoporosis at very high levels, such as 45 mg per day.
7:50 We know that MK7 has a longer biological half life than MK4 and it has been claimed that this is why MK7 is more effective, but just because we see a higher level in the blood stream does not mean that it is more effective. We often measure certain nutrients in the blood, such as calcium, but this does not tell us if the calcium they are taking is effective. What matters is the amount of the nutrient in the tissues and not in the bloodstream. And just because MK7 persists longer in the bloodstream doesn’t mean that it is more bioavailable. In fact, it may persist in the blood longer because it is not readily taken up by the tissues.
11:14 While vitamin D status is accurately assessed by serum tests, many serum tests of vitamins, such as serum calcium, are not good measures of calcium status in your tissues like your bones. While serum vitamin K tests may have some value and levels do go up after supplementing, but since vitamin K1 and K2 are transported by triglycerides and by lipoproteins, levels of triglycerides may affect the test results. And you would certainly not want to use serum tests of vitamin K1 to guide coumadin levels and in fact you should not supplement with vitamin K if you are taking coumadin, which is a blood thinner used sometimes to reduce clotting.
15:54 How vitamin K affects bone formation both in young people and also in post-menopausal women and older men, esp. those who see a decrease in testosterone levels, who tend to see a decline in bone health. The average intake in the US of vitamin K1 is only 90 mcg, which is not even enough to meet the minimal amount of 120 mcg needed for clotting. And research indicates that we need a lot more to support the rest of the body, including the bones, the arteries, and the brain. There is a protein–Osteocalcin, whose job it is to bring the calcium into the bones. Matrix GLA is a protein which is supposed to prevent the calcium from going into the soft tissues like the arteries. When these proteins are activated, this is called carboxylated. When we have enough carboxylated matrix GLA from having enough vitamin K, we will prevent heart valve calcification, kidney stone formation, and even the lungs can become calcified and have lower elasticity. We tend to focus on preventing the calcification of the artery walls, which is different than the calcification of the plaque. It would be good if we could measure uncarboxylated osteocalcin and uncarboxylated matrix GLA, but these tests are not currently available in the United States. With bone, the calcium is built on a collagen matrix, so proper collagen synthesis is also very important for bone health.
21:02 Vitamin D. Vitamin D works closely with vitamin K to transport calcium from your intestines into the blood and into the bone. To optimize bone formation you need optimal levels of vitamin D, vitamin K, calcium, magnesium, and phosphorus, all of which are deposited in the bone. And bone is built on a matrix of collagen, which is like the steel rebar that makes the concrete stronger, so we should optimize the intake of collagen and all of the above vitamins and minerals. This can be helped with collagen supplementation as well as vitamin K, which stimulates collagen synthesis. The collagen does not increase bone density but it makes the bone stronger and more resistant to fracture and bone fragility can be measured with quantitative ultrasound. Studies that have show reduced fracture risk have used K1 at 5 mg and MK4 at 45 mg. Designs For Health offers 1 mg of vitamin K1 and 1 mg of MK4 in their Vitamin D Supreme product and then if you are older or have increased risk of bone loss, you can add the 2 caps of Tri-K that adds an addition 4 mg of K1 with 1 mg of MK4 and 35 mg of geranylgeraniol, which is equivalent to 45 mg of MK4.
27:09 Both K1 and MK4 have some positive benefits in bones and arteries and both K1 and MK4 can carboxylate (activate) osteocalcin and matrix-GLA. Eventually in most tissues all forms of vitamin K, including MK7, are converted into MK4 for storage, though this depends upon the organ. For example in the arteries, 25% of vitamin K is stored as K1 and 75% as MK4, and in the brain 90% of vitamin K is stored as MK4, though in the heart 90% is deposited as K1 and only 10% as MK4. There are a few rat studies where they were flooded with the equivalent of 60 mg of MK7 and this dosage overwhelms the capacity of conversion, so a lot gets deposited as MK7, but this is not a normal physiological condition. When we give MK7, the uptake is slow because it is slowly converting to MK4, which we thought was beneficial, but then we saw the results of the studies with MK7 that did not do better than the interventions with K1 and MK4 and MK7 is 50 to 100 times more expensive than K1, so it is not worth it. It is better to provide K1 and MK4 and then add some GG, which the body uses to convert K1 to MK4. From an evolutionary point of view, we have consumed about 1 mg of K1 from fruits and vegetables and a smaller amount of K2 from meats and fermented foods.
31:23 Some would argue that the reason that the Japanese have better bone density than in the US is because they consume natto, which contains MK7. Only some of the population consumes natto, since it is not a very tasty food. The average K2 intake from natto was about 57 mcg of MK7 and natto not only contains MK7 but also genistein, which is a phytoestrogen that stimulates the estrogen beta receptors and can be beneficial for bone health. So the genistein may be at least partially responsible for the bone building properties of natto. Studies that have looked at using 180 or 360 mcg of MK7 did not show positive results. One study using 180 mcg of MK7 did show a slower decline of bone density than placebo, but we are looking for a way reverse the loss of bone density and not just slow the decline. unfortunately a number of the studies that have looked at vitamin K for bone density have not provided enough vitamin D or enough calcium or magnesium and few studies have included resistance exercise. One study that used vitamin K in Greece did use 1000 mg of calcium and 393 mg of magnesium and vitamin D and there was an increase of 1.3% in bone density.
36:10 Cristiana recommends for bone health to supplement with a minimum of 1 mg (1000 mcg) of K1. If there is osteopenia or osteoporosis, she recommends 5 mg of K1 along with some MK4 and GG or you can use the Japanese approach and take 45 mg of MK4. In addition, you should supplement with vitamin D, an absorbable form of calcium, magnesium, vitamin C, zinc, silicon, sulfur, and collagen. You should also follow an alkaline diet and do resistance exercise.
39:48 Vitamin K can reduce cardiovascular disease, including arteriosclerosis, which is the stiffening of the arteries due to a deposition of calcium in the arteries. Interventions with 2 mg of vitamin K1 have shown reduced arterial calcification by 45%. Studies with MK7 have not shown a reduction in arterial calcification, while studies with MK4 have shown a 18% reduction in arterial stiffness and one study with MK7 showed reduced arterial stiffness by 6%. The mechanism by which vitamin K can reduce arteriosclerosis is by carboxylating MGP, but we do not have a commercially available test for uncarboxylated MGP in the United States. We do not have studies showing whether K1, MK4 or MK7 are better at carboxylating MGP. The recommendation is for reducing arterial calcification is to supplement with at least 2 mg and up to 5 mg of K1 and then you would want to add some GG to help with the conversion of K1 to MK4, which is the form it is stored in in the arteries. We need to point out that this arteriosclerosis is separate from the atherosclerosis from the calcified cholesterol plaques that build up in the artery walls. This process involves the penetration of oxidized LDL and foam cells, etc. There is a form of vitamin called tocotrienols which have been shown to reduce arterial plaque and there is a supplement that contains rhamnan sulfate that can reinforce the arterial wall called Arteriosil. By reinforcing the layer of the endothelium called the glycocalyx, we can reduce the penetration of the oxidized LDL and it may even cause regression of the plaque.
Cristiana Paul has a Master’s in Nutrition Science from Cal Poly Pomona and she has extensive experience in clinical practice and reviewing nutrition research. Cristiana wrote chapters on omega-3s and vitamins K forms, in the 2012 and 2020 editions of Textbook of Natural Medicine, edited by Dr. Joseph Pizzorno and Dr. Michael Murray. Cristiana is the author of peer reviewed papers on topics such as inositol’s roles in insulin resistance/PCOS, a new view of collagen protein in human nutrition, nutritional approaches to managing inflammation, and metabolism of B12 forms in the setting of various genetic polymorphisms. She is currently working on a paper exploring the rationale for supplementation with Nicotinamide Riboside to support healthy aging. She is an independent researcher and has been a scientific consultant for for the past 20 years for Designs for Health, a professional line of nutritional supplements, where she has contributed to position papers as well as helping to develop products and nutritional protocols. Designs For Health supplements are sold through licensed doctors and practitioners like myself.
Dr. Ben Weitz is available for Functional Nutrition consultations specializing in Functional Gastrointestinal Disorders like IBS/SIBO and Reflux and also specializing in Cardiometabolic Risk Factors like elevated lipids, high blood sugar, and high blood pressure and also weight loss and also athletic performance, as well as sports chiropractic work by calling his Santa Monica office 310-395-3111. Dr. Weitz is also available for video or phone consultations.
Dr. Weitz: Hey, this is Dr. Ben Weitz, host of the Rational Wellness Podcast. I talk to the leading health and nutrition experts and researchers in the field to bring you the latest in cutting edge health information. Subscribe to the Rational Wellness Podcast for weekly updates. And to learn more, check out my website drweitz.com. Thanks for joining me and let’s jump into the podcast.
So hello, rational Wellness podcasters. I wanted to let everybody know that while many of my podcasts involved a discussion of scientific and medical research, this episode is going to go really deep into the science of vitamin K. If you find the level of scientific detail challenging, please check out the show notes on my webpage, dr weitz.com, where you can find a summary of some of the important points discussed as well as a full transcript. And I’ll also include some of the references. So I’m very excited today that we’re going to be interviewing Cristiana Paul on vitamin K.
Everyone has heard a lot in the last five years, or at least many of us have, about the potential benefits of vitamin D. But the new kid on the block, vitamin K is getting increasing attention as a super important fat soluble vitamin. The research and potential benefits of vitamin K is fascinating from promoting bone health to reducing the progression of arterial calcification to a whole host of other potential benefits. But there are some controversies concerning vitamin K, including how much and which form is best to take, K1 or the two commonly commercially available forms of K2, MK4 and MK7? I have been convinced that the MK7 version of vitamin K was the best form to take since it is known to have a longer biological half-life than MK4 and several prominent integrative cardiologists have recommended this form, including Dr. Steven Sinatra, who recently passed, and who recommended taking up to 360 milligrams of MK7, I think micrograms of MK7 for reducing arterial calcification. I recently attended the Cassie Education Conference sponsored by Designs for Health, where Dr. Barry Tan spoke and mentioned that we should stop taking MK7 and that MK4 was a more natural form. So I had to learn more why he said this and what the truth is based on the latest scientific research, which is why I have asked Cristiana Paul, product development consultant for Design for Health and expert on vitamin K research, to join us today for a discussion on vitamin K.
Cristiana Paul holds a master’s in nutrition science from Cal Poly Pomona and she has extensive experience in clinical practice and reviewing nutrition research. Cristiana wrote chapters on Omega three and vitamin K in the 2012 and 2020 editions of the Textbook of Natural Medicine edited by Dr. Joe Pizzorno, who’s a member of the board of directors for the Institute of Functional Medicine and who we have had on the podcast multiple times. Cristiana is the author of peer reviewed papers on topics such as the role of inositol in insulin resistance in PCOS, a new view of collagen protein in human nutrition, nutritional approaches to managing inflammation, and the metabolism of vitamin B12 in the setting of various genetic polymorphisms. She’s currently working on a paper exploring the rationale for supplementation with nicotinamide riboside to support healthy aging. Cristiana is an independent researcher and she’s been a scientific consultant for the past 20 years for Designs for Health, a professional line of nutritional supplements. There she has been contributing to position papers as well as its development of products and nutritional protocols. Cristiana, thank you so much for joining us today.
Cristiana: You’re welcome. I’m excited to be here and share my opinion on research. This research and all nutritional research is fast evolving, as we all know. It’s hard to keep up with all of it. I used to be in clinical practice for about 10 years, but then I shifted into just doing nutrition reviews because that’s a full-time job for sure, and I can’t even say that I’m an expert in every topic, but I did dig into this topic. I started in 2000, about 2010, 11, when all of a sudden we became aware of the effects of vitamin K beyond the clotting. We all knew that we need a little bit of vitamin K in multivitamins, in the diet to ensure that we have adequate clotting. And at that time, MK7, it was kind of a new kid on the block promoted by manufacturers that had had a patent on it. And so it was a branded form of vitamin K, MK vitamin K2. Although the research on MK4 has been going on in Japan for at least 30 years, but we were just not as much aware in US of how the Japanese were using MK4. Actually at very high doses for osteoporosis. So that knowledge…
Dr. Weitz: What do we care what the Japanese are doing, we’re Americans.
Cristiana: You know what, it’s amazing how advanced they are. And also collagen, it’s interesting because I read and now we know collagen is involved in bone strength and it works together with vitamin K, and they were advanced in that realm of research as well. So I dove into it because MK4 and K1 are not branded ingredients. Nobody’s really promoting them as heavily because there’s no patent on them necessarily. So I had to review all the research. I published the 2012 review, but at that time we didn’t have enough intervention studies on all these forms. So 2020 review I feel is much more comprehensive. And then since then there’s still more studies published on vitamin MK7 and so on. So today we’ll try to outline what we know today and then you see in the market, a lot of companies are using just MK7 or just MK4 or combination of two or three of them. And as I advised Designs for Health the last 10 years, the formulas have changed based on what we’re learning.
Dr. Weitz: So we have K1, we have MK4, we have MK7. There’s a lot of confusion as to which is the most important one. Should we be taking all three of them? Should we be taking mostly K1? Should we be taking mostly MK4, MK7? We know that for example, vitamin K1 plays, or at least as it’s been told, that vitamin K1 is the main form of vitamin K related to clotting. We’ve been told that MK7 has a longer biological half-life, so I think that’s where some of the thinking that vitamin MK7 is going to be more effective if it’s sticking around longer. But interestingly, there are nutritional compounds that are not in the body very long and actually are extremely important. And I recently learned that nitric oxide is actually a gas and is only around for seconds and yet has this incredible amount of biological activity.
Cristiana: Yeah, you’re right. And we have to really understand the basics. Let’s say doctors measure plasma calcium, and that’s a typical blood test. But if I measure plasma calcium, that doesn’t tell me if this person has good bone density, if they’ve been taking calcium for a while, if they have good calcium in their muscles for contraction. So if I took plasma calcium and I measured plasma levels, they’re not going to stay high for very long because the body has a way to take the calcium into the tissues. And also there’s hormones like parathyroid hormone and so on that regulate levels of calcium. So it’s the same thing with vitamin K. You can take vitamin K, all three forms, and we can follow what happens. How long would K1, K2, whether it’s MK7 or MK4, how long would they last in the bloodstream? So which means when you look at bioavailability, because people worry about is this supplement bioavailable? Well I see that it’s absorbed right away, but then it’s also taken up by the tissues. So after one time administration, yes there was a study show that MK7 lingers longer, but that doesn’t mean it’s more bioavailable. It almost looks like it’s harder to being taken up by the tissues. But regardless, I mean I don’t judge the effectivity of vitamin K forms based on plasma levels. I also need to tell everybody that I looked at studies after supplementing for months with all three forms and plasma levels do go up. It’s kind of an indicator. These studies looked at plasma levels almost to see compliance, that people were taking these vitamins. But they measured other markers of vitamin K status, which I’m going to explain.
Dr. Weitz: And by the way, Cristiana, I’d just like to point out for those who aren’t aware, this is pretty common that there are a number tests you can do to measure serum levels of, you mentioned calcium, you mentioned a number of vitamins. And for the most part these serum tests are really worthless. That’s why researchers have come up with much more complicated ways, more functional tests to measure the status of these vitamins. Vitamin D test, the serum is an exception, but for the most part, serum calcium tells you nothing about the calcium status in the body. The person could have osteoporosis and they could have a normal serum calcium. So if you’ve been to your doctor and he says you don’t need calcium because you have a normal calcium serum level, it means nothing. And ditto for serum B12 and a whole bunch of other vitamins.
Cristiana: Right. So unfortunately these tests are new. The tests for vitamin K status, which I’ll explain what that is, they’re new and labs like Quest and so on, they’re not performing those. We need to go to specialized labs for vitamin status. And that’s why that whole idea of the way the vitamin MK7 was promoted, there’s more quote-unquote “bioavailable” based on plasma levels. It’s not a valid argument. And it’s not even true after you supplement longer with these vitamins. It is an indicator. And also keep in mind that these vitamins, vitamin K1 and MK2 are transported by triglycerides and by lipoproteins. So if somebody had higher levels of triglycerides, it’s going to look, like K1, let’s say it’s higher, so you would have to in research divide by K1 to get a sense. Now some doctors that monitor patients on Coumadin, which is working to block vitamin K, they do those measurements to get an idea maybe of how much vitamin K the patient takes. They have to be careful with vitamin K from diet and supplements. So we’re not going to really go into management of patients on Coumadin because that is a very, very tricky situation and you have to be monitoring INR with a doctor and with the conditions. So we’re not recommending that those patients take vitamin K supplements unless the particular doctor that monitors them with whatever tests, and I think some of the tests would be plasma K1 at Quest let’s say. But if they decide to supplement with a little bit, maybe a hundred micrograms. The idea was to keep the plasma levels more levels so that you don’t have to be affected by greens that contain vitamin K1 because it’s a pity to tell the patients not to take those healthy foods. So that is a complicated situation. We’re going to talk mostly about…
Dr. Weitz: Okay, Cristiana, let me just clarify for everybody in case you didn’t follow what she just said. There are some patients who are being prescribed Coumadin. These are typically patients who have blood clots or at risk of blood clots or who’ve had a stent. And they’re worried that there’s going to be a clot. Sometimes patients with arrhythmia, they’re often prescribed a blood clotting medication. And for many years Coumadin or warfarin was the most commonly prescribed one. Doctors are starting to use Coumadin or warfarin less frequently. But the way that drug works is by blocking vitamin K and that’s how it reduces clotting. And so then the issue is if you’re taking a drug to block vitamin K, why would you want to take vitamin K at the same time? That’s going to uncouple the effectiveness of the blood thinner.
Cristiana: And then there’s alternative blood thinners that promote the idea that you don’t have to be worried so much about vitamin K from foods and possibly from supplements. But then again, we’re not going to talk today so much about those situations. We want to talk about how vitamin K affects healthy people, younger women, younger men and teenagers obviously that need to build bone. And also in the later stages of life where women have an increase in bone breakdown due to lack of lower hormones, whether they take hormones or not, you have an increased breakdown of bone and that balance between bone breakdown and bone rebuilding is tilted towards bone breakdown. And in case of men, some of the men have a decline in testosterone and that affects the bone health as well. And also exercise weight training that sometimes is not done properly as we get older due to various reasons and that’s going to affect the bone as well.
So I would like to start by saying that the average intake in US of vitamin K1 is 90 micrograms. And it’s in a range from 30 to 222 micrograms. We need for clotting, we need about 90 or 120 depending on the body size of female, male. Let’s say 120. This tells me that maybe half the population doesn’t even take enough vitamin K1 to support adequate clotting. Basically the liver stores, as you take vitamin K1, stores vitamin K to activate the clotting protein. So there’s a deficiency there for that. But all the research points to the fact that we need a lot more to support the rest of the body. The rest of the body, the bones, the arteries, the heart, the brain, the testes been shown to store a lot of vitamin K. And the question is why? And we found out some of the facts, we don’t know all of them, but the research is trying to figure out what is the optimal amount of vitamin K1 and/or K2 to support all these proteins that do a very important job. One protein is to bring the calcium into the bone, that’s called osteocalcin. I’m going to call it bone transport protein. Then there’s other proteins, they’re called matrix GLA, that’s the chemical name, I’m going to call them guardians of the arteries, guardians of the galaxy. They make sure that there’s…
Dr. Weitz: By the way, there’s a new Marvel movie coming out called Guardians of the Arteries.
Cristiana: So what they do is they keep calcium from going in the wrong place. For some reason if they are not armed with the weapons and the weapons are actually these claws made by vitamin K, you can think of their swords. So the more swords they have from vitamin K, the more efficient they are to keep calcium from going into the arteries, into the heart valves because the heart valve gets calcified, into the kidneys. Kidney stones. Now we think that even the lung is affected also calcified and lower elasticity when you don’t have enough vitamin K. So we focus on arterial calcification because that’s such a common concern as we get older and it’s the calcification that occurs inside the arterial wall. That’s not the calcification of the plaque. There’s two areas where calcium goes in and causes issues. So vitamin K at about one milligram, I’m going to make the case from studies, it’s probably pretty good amount to completely activate those bone transport proteins. It’s like an excavator that has teeth, right? And if you have more vitamin K, you have all your teeth on that excavator. If you don’t have enough teeth on the excavator, you can’t grab enough calcium from the blood to put it into the bone. So it’s activating these proteins, the more you have. So we can measure that in the blood. That’s called the level of carboxylation. It’s basically the level of activation of these bone proteins. Same thing with the guardians of the arteries. They also have these swords or claws that they keep the calcium and they are also activated. We can measure that. Unfortunately that’s a test only available in England right now for the MGPs. But osteo calcium and carboxylate osteocalcin was at least available from one lab. I’m not sure if that’s still available, but maybe other labs will pick up that test in the US. And that is truly telling you if you have enough vitamin K in your body.
Vitamin D works closely with vitamin K. Vitamin D helps with transport of calcium from your intestines into the blood. It also vitamin D upregulates the making of these proteins. So how many of these bone transport proteins you have and how many guardians of the arteries you have is determined by your vitamin D level. So you have to supplement, you try to optimize your intake of vitamin D and also vitamin K, also intake of your calcium, magnesium, phosphorus, all these are deposited in the bone. So unfortunately the studies did not optimize vitamin D. We look at all these studies and we know that vitamin D awareness is relatively new. Some of the studies they just gave vitamin K but they didn’t, they barely gave 400 IUs of vitamin D. So it’s hard to achieve a result when you don’t give enough. The Japanese with their studies have given some vitamin D, but at the time D3 was not available in Japan. They were giving the active form of D as a drug. So that’s unfortunate. So again, in our clinical practice we tried to optimize all these factors. And on top of it is collagen story. When you have concrete walls built, you put rebar, you put a mesh of steel or a bone to support that concrete. So the bone is not just bricks piled onto each other, they are supported by this collagen mesh. And so now we became aware of collagen supplementation, but also the fact that MK4 stimulates the formation of collagen. So in the bone and in somewhere else in the body possibly. So we have to look at the big picture, as practitioners you have to look at all these aspects, the intake of calcium, the intake also…
Dr. Weitz: Cristiana, let me stop you for a second. So you mentioned how vitamin K stimulates collagen synthesis. Is this one of the reasons why some of the studies on the benefits of vitamin K for bone seem to have a stronger effect on reducing fracture than they do on increasing bone mineral density?
Cristiana: Absolutely right. Very good point. Because when we measure bone density, we don’t get the whole story. As you know, biphosphonates could possibly increase or maintain bone density because it shuts down the bone breakdown. But it doesn’t support bone buildup. So some people actually measure bone elasticity through bone ultrasound. Some tests are out there for that. And at the end of the day what you worry about is risk of fracture. So we’re looking at what studies and what forms of vitamin K have shown reduced risk of fracture. So we have that with vitamin K1 at five milligrams and we have that with MK four at 45 milligrams reduction in fracture.
Dr. Weitz: Now by the way, both of those numbers you just mentioned are quite a bit higher than the amount of K1 or K2 that most people supplement right now, isn’t that correct?
Cristiana: Yes and no. So vitamin K1, for example Designs for Health, is offering a foundational formula with K1 at one milligram and then MK4 at one milligram, in addition to vitamin D. Because that’s your foundational supplement. And when you are younger and your hormones are good and exercising, you don’t maybe need to take those higher doses. When you are older, that’s when the higher doses come in and they act a bit differently. I mean in addition to activating those bone transport proteins or the guardians of the arteries, we have an effect from MK4 on a pathway that’s known as HMG co-a where cholesterol medicine acts and where bisphosphonates act, where CoQ10 is made. So when we act on that pathway, we have an additional ability to reduce bone breakdown. So that’s why we need the higher doses. Now instead of using the 45 milligram of MK4, also the Japanese have pointed out that it’s really the geranyl component of MK4 that may act at that high dose. And so that would be equivalent to about 30 milligrams of geranylgeraniol, which is available as a supplement from Designs for Health. And it was added to the additional Tri-K formula. The idea was younger people that are in good shape, it can take their vitamin D plus the one milligram of K1 and one milligram MK4 because K1 converts to MK4 to a certain extent. But when you’re older, on top of that you may want to add another four milligrams of K1 and another one milligram of MK4 and the geranylgeraniol at 30 milligrams or 75 milligrams, the double dose.
Dr. Weitz: Now let me just stop you one second again. Sorry for keeping interrupting you.
Cristiana: No, you can interrupt me to clarify.
Dr. Weitz: So you’re mentioning vitamin K1 and you mentioned how it converts a lot of times into MK4 because MK4 is the most common storage form in most of the organs in the body, except for the liver. Now do we know, is K1 actually having the beneficial effects on bone and arteries or is it MK4 that is being converted? Is K1 converting into MK4 that’s having the effect or are they both having an effect?
Cristiana: That’s a very good question. And the thing is both. If you test it in vitro, both K1 and MK4, they carboxylate these proteins, they activate these proteins. When it comes to absorption, when you absorb K1 or MK4, the body converts some of it. Let’s say 25% of K1 stays at K1 and is deposited in the bone. 75% is deposited as MK4. We don’t know, I mean they both carboxylate, we don’t know why that each tissue has its own ratio. In the heart, for example, 90% is deposited as K1 and 10% as MK4. In the arteries we have the 25% K1 and 75% MK4. So it’s interesting that in the brain…
Dr. Weitz: And is MK7 also converting into MK4?
Cristiana: Yes. So what studies have found at the doses that were given, equivalent to the nutritional doses, the body attempts to convert all vitamin K2 forms. It’s MK6, 7, 8, 9, 12. They are converted to MK4 before being deposited in the tissues. If you flood the system like some rat studies gave the equivalent of 60 milligrams of MK7, it overwhelms the capacity of conversion and is deposited as MK7. But for our purposes, when we look at deposition of MK7 given at the level of 180, 380 micrograms per day, those are most likely just converted to MK4. But it’s converting it slowly. The uptake is slow, it’s converting it slowly. Is that necessarily a benefit? We thought so maybe a long time ago, but when we saw the results from interventions with MK7, they did not do better than the interventions with K1 and MK4. And it’s a much more expensive ingredient, about 50 to a hundred times more expensive than K1. So why use that ingredient when you can achieve all the other goals with K1 and also you provide MK4 in case there’s not enough conversion from K1 to MK4, you provide also the GG molecule which the body needs to convert K1 to MK4. So that’s the thing. We don’t know which one does it. And sometimes people say K1 is the most, MK2 is the most important. You can say it’s most important because 90% of the body deposits K2 as MK4. But K1 seems to be preferred in some tissues and we don’t know and that’s why we want to supplement, it’s less expensive. And also from a physiological, evolutionary point of view, throughout evolution our bodies were exposed to K1 and K2, but K1 at a level about one milligram per day from fruits and vegetables. And K2, some from meats and so on, fermented foods. So in a way you are supporting what the body is adapted to. And I’m a firm believer in evolutionary medicine, evolutionary nutrition.
Dr. Weitz: Now some people would argue that when you look at the Japanese that consume fermented soybeans known as natto, which contains MK7, they have better bone density and that is part of the argument for MK7. What say you to that?
Cristiana: So yes, I looked at those studies. The average intake was about 57 micrograms of MK7. Only certain people consume natto because it’s not a very tasty thing. And the range was, I mean, the total vitamin K2 was about 61 micrograms. Some people ate as much as 200 micrograms, the intake in Japan. But natto is a very high source of genistein, which is a phytoestrogen. Because it’s formative from soy and rice. And we know from studies with genistein, that that alone has a tremendous effect on bone health, improving bone density or delaying bone loss during menopause, because genistein acts kind of like estrogen on estrogen beta receptors, not alpha. Which makes it safer when it comes to worries about breast cancer and other gynecological cancers.
But we have that component that people don’t mention, you know, you can’t attribute the high bone density just to the 57 micrograms of MK7. And when we did interventions with 180 and 380 micrograms of MK7, we did not see good results. For example, two studies show that used 360 micrograms and 370 micrograms of MK7 did not slow down bone density decline compared to placebo. They had one study with 180 micrograms of MK7. One showed that the decline was a little slower than placebo and the other study showed that it was the same. Now even if I slow down a little bit the bone loss, that doesn’t mean it’s a solution for me. I don’t want any slowdown. I want to hopefully go back, I mean maintain or increase it back. So it’s possible that these studies also were flawed because they didn’t provide enough vitamin D and K and so on. It’s interesting that one study used a hundred micrograms of K one and also compared with 100 micrograms of MK7. This was a study performed in Greece where they had higher intake of calcium, about a thousand. And then they gave magnesium, which very few studies did. 393 milligrams of magnesium. They gave vitamin D, but in Greece they like to go in the sun. So they have higher levels of vitamin D probably in the blood. And they exercised. Very few studies imposed exercise. So that study achieved an increase in what, 1.3% in bone density. But that also shows you that K1 and MK7 did the same. So why should I use a much more expensive vitamin if I can achieve the same with vitamin K1? And that doesn’t tell me though that I only need a hundred micrograms of K1 because I know that for complete carboxylation I need about a thousand. It’s great that they achieved that particular result. But looking at all the other studies, we advocate a thousand micrograms, which is one milligram of K1. Another issue that came up in the news a lot was when you take vitamin D and calcium, you’re going to increase arterial calcification. People were saying, well you have to choose between your arteries and your bones. If your bones are bad, then take calcium. If your arteries, don’t take it. We don’t have to choose because they forgot about vitamin K. Right? So there was a beautiful study where they gave vitamin calcium and vitamin D, but they gave one milligram of K1 with it. And it showed that it did not increase arterial stiffness. Which is kind of a surrogate for arterial calcification. And then we have studies that looked at arterial calcification with K1 and also with MK7. MK7 did not reduce the progression of arterial calcification.
Dr. Weitz: So let’s just finish up on the bone part first. What would you say would be an optimal set of recommendations? Obviously every person’s different, diet, other factors, but just some kind of general guidelines for a program to improve bone health, say in a postmenopausal woman who has osteopenia.
Cristiana: So she would have to take vitamin D, obviously, to an optimal level and that’s debatable, but let’s say middle of the reference range, upper zone of that reference range. In addition, I would say a minimum of one milligram of K1. But if the situation is bad and we need to reverse osteopenia, osteoporosis, I would recommend the full five milligram dose of vitamin K1. So you would take, let’s say one milligram from your base formulation and additional four milligrams. That gives me confidence that I have complete carboxylation and I have a chance to reduce bone fracture. Now when it comes to MK4, you want to provide some MK4 preformed, but you can take the GG, which is the active portion of that MK4, at at least 70 milligrams, and then you could choose to do the 45 milligrams MK4 as an alternate because that was the Japanese approach. It’s more expensive. So doing it the other way with GG is a more affordable way to try to achieve a similar effect on reducing the excessive rate of bone breakdown. That’s what we’re trying to affect both sides of the equation. We’re trying to build bone, support everything that brings calcium in and also reduce bone breakdown.
Dr. Weitz: And would you think that the data would also support a certain level of supplementation of a highly absorbable form of calcium as well as magnesium?
Cristiana: Yes, absolutely. Yeah. The chelates seem to have a much better absorption. They absorb on the amino acid pathway, they’re not affected by other components in food and it will not cause constipation or diarrhea and so on. So the chelates are a better option supplementing with collagen. Now collagen metabolism, just because you provide collagen doesn’t mean the body’s going to deposit the right amount because you need vitamin C for collagen formation. The hydroxylation, you need silicone and you need as well other components, even zinc and sulfur. So the vitamin C and silicone are crucial for collagen formation and having adequate amount of collagen as part of your diet based on your body size. And then of course, fruits and vegetables to make sure you have an alkaline diet. Exercise. Very important, to the type of weight resistance exercise.
Dr. Weitz: Let’s focus for a little bit upon the cardiovascular aspect of this discussion. How vitamin K can help to reduce the potential for cardiovascular disease. And something you just happen to mention that I think most people probably missed is you said there’s a difference between calcification of the plaque and the calcification of the artery. So let’s make sure we include that in this part of the discussion please.
Cristiana: Yes. So as most people know that as we get older there’s an increase in blood pressure, increase in arterial stiffness. The blood vessel don’t dilate very well, which makes it harder for the heart to pump blood. And it’s called idiopathic increase in blood pressure. And so why is that happening? It’s that deposit inside, if you think of the artery, it’s layers of muscles and collagen. And so inside there, there’s a deposition of calcium, which is inadequate. And if we have adequate amount of vitamin K. Now, is it K1 or K2? It’s not clear which one is more important, but we know that the interventions with vitamin K1 at two milligrams have reduced arterial calcification progression by 45%. It didn’t stop it, but it reduced it by 45%. If you only gave 500 micrograms of K1, it reduced it by 6%. So the two studies with 360 of MK7 did not show a reduction in arterial calcification. The blood test would be very useful because if we see the levels of, it’s called MGP, decarboxylated dephosphorylated MGP, that level, you want it to be as low as possible. The more vitamin K you give, and now we have evidence for K1, the better we are to lower the inactive soldiers, so to speak. Right? So unfortunately we don’t have studies with MK4 for that particular blood test. I hope they will do them. What they showed with 45 milligrams of MK4, they reduced arterial stiffness by 18%. And then MK7 had one study with reduced arterial stiffness by 6%. So not as much. So again, if I were to choose to reduce arterial calcification, improve arterial stiffness, I can go as high as two milligram of K1 based on studies. I could go to the five milligram, which I’m using for bone anyway, right? There’s no toxicity to vitamin K1. And then you want to add the GG to help with that conversion from K1 to MK4, which we see in the arteries and in the heart. There’s different ratios between K1 and MK4.
Dr. Weitz: Now can vitamin D also play a role in reducing coronary calcification of coronary plaque?
Cristiana: Vitamin D helps to upregulate the expression of these guardians of the arteries, right?
Dr. Weitz: No, no, I meant vitamin K, I’m sorry.
Cristiana: Oh, vitamin K.
Dr. Weitz: Yeah. Because you’re talking about how it reduces calcification of the arteries and you’re saying that’s different than calcification of the…
Cristiana: Of the plaque.
Dr. Weitz: The calcified plaque, the atherosclerosis.
Cristiana: Yeah, yeah. In rats, yes, they’ve shown some effect of very high doses, but we haven’t seen that in humans. And the arterial plaque is a very complex process and it involves the penetration of oxidized LDL and oxidized and causing the foam cells and so on. I think we have many other nutritional tools for that. Vitamin K may help a little because it reduces inflammation. So it’s possible. But we have, for example, a special form of vitamin E called tocotrienals, which had some studies that showed a reduction in arterial plaque. And also we have a very novel new intervention on the glycocalyx of the arteries. This is something that, it’s very exciting, a new way to look at the health of the arterial wall. And if we reinforce that arterial wall with things like rhamnan sulfate, it’s a seaweed that’s now offered as a supplement called Arteriosil. If we offer that to constantly reinforce that endocalyx, that layer, some studies have shown that reduces the penetration of oxidized LDL, the progression and some even case studies showed regression of that plaque. So I don’t know that the vitamin K has a huge role in that part of calcification and arterial plaque. And then the discussion is more complex because we talk about the vulnerability of the plaque.
Dr. Weitz: Right, stable versus unstable plaque and yeah…
Dr. Weitz: Yeah. Yeah, we’ve been using that arteriosil product for a bit in the office here. And yeah, there’s actually some controversy in there can be an argument that in some cases having calcified plaque makes the plaque more stable and less likely to cause a heart attack or stroke.
Cristiana: I know there’s that controversy, but if you address this process where…
Dr. Weitz: Bottom line it’s better not to have any plaque, of course.
Cristiana: Any plaque and then, yeah, I don’t know that vitamin K affects that particular calcium. Another issue with the statins, because statins are advocated as stabilizing plaque and lowering cholesterol and all those lowering inflammation and so on. But a problem with statins is that it blocks the formation of geranylgeraniol this molecule that helps the body convert K1 to MK4. It’s similar to what happens to co-enzyme Q10. Everybody knows that when you teach patents you reduce coQ10, same pathway…
Dr. Weitz: And you reduce vitamin D and you reduce a whole series of things.
Cristiana: And so they found studies where a correlation between taking statins and increased arterial calcium scores. And again, where is that calcium? Is it in inside the arterial wall or is it in the plaque? Right? Because when you do a calcium score, you can’t separate. Now there are some arteriosil planning study in China. There are some university based studies where they look at the plaques separately. It’s kind of like an MRI of the plaque so we can see exactly what kind of plaque you have. Is it calcium there? And so you can separate the calcium from outside the artery from the inside the wall.
Dr. Weitz: And one study that just came out recently showed that statins actually increase lipoprotein A levels, which is a particularly atherogenic particle. And so even though they lower LDL by raising lipoprotein A levels, they may actually play a role in plaque risk as well.
Cristiana: And actually tocotrienol administration was shown to reduce lipoprotein, interestingly enough. So you’re right, the story with the statins is interesting, but I think that by supplements…
Dr. Weitz: Also maybe we shouldn’t put it in everybody’s water.
Cristiana: Yeah, I would try all the natural supplements first before going there. I know it’s interesting now that we have this tool to add GG, even if you were to take a statin, if a doctor doesn’t want to take a chance and gives patients a statin. By adding that GG to the regimen, it’s not going to affect cholesterol levels. But then it gives you the opportunity to make intracellular levels of CoQ10, which may even be more important than exogenous supplementation of CoQ10. And it gives you the opportunity to affect at least the calcification inside the arteries. Which can be good because if you have stiff arteries, you have higher blood pressure, more risk for stroke and so on. So maybe the calcium in the plaque may be protected but the calcium inside the arterial walls is not good.
Dr. Weitz: And stay tuned to the Rational Wellness podcast because in a few weeks we’ll have Dr. Barry Tan on and we’ll be discussing GG.
Cristiana: That’s great, that’s great. It’s a very exciting new molecule to consider for many aspects of health, mitochondrial health and so on.
Dr. Weitz: So let’s talk about some of the other benefits of vitamin K. There seems to be some data that maybe it could play a role in reducing the risk of kidney stones.
Cristiana: Right, right. Because it’s the same type of molecules. MGP are involved in how calcium is metabolized there. So now when you look at studies with nutritional supplement interventions for kidney stones, magnesium is very important. Drinking enough water, the balance of calcium and magnesium is important and we know how deficient most people are in magnesium. But yes, vitamin K, when you optimize it everywhere in the body, everything works better. You were interested in maybe brain effects and nerves. For some reason there MK4 is deposited at much higher levels than K1. And they had a study with rats where they gave K1 or they gave MK4 preformed. And it turned out that the supplementation with K1 increased MK4 brain levels better. And why is that? You would think… Because MK4 is not all taken in and deposited unchanged. For some reason the body breaks down K1 and MK4 to a water soluble molecule. The core molecule, menedione, which is called vitamin K3.
And that water soluble molecule is able to get in through the blood-brain barrier. And there the body makes MK4 from this K3, which means it needs GG. so if you are taking a statin or bisphosphonate, you are going to be deficient in GG. And I think there was some association with statins and dementia and so on. So MK4 is important for nerves, for myelin production. It seems to have an anti-inflammatory effect in some autoimmune conditions in some animals.
Dr. Weitz: Yeah. You mentioned that MK3, it’s kind of interesting, I guess some of the MK1 gets converted to MK3 and then into MK4, right?
Cristiana: Right.. For some reason you can think of vitamin K as like a key chain. The core chain is the molecule that carboxylates, but it has various, we call them ligands. So you can have various tails, various keys on this chain. So there’s a key specific for K1, there’s a key for MK4, it’s four units length of isoprentanol units. We don’t need to go into the chemical names, but the MK7 molecule tail is a little longer. So that’s why we call them MK6, 7, 8 to 12 because they have longer tails. But the body has a way, even when you absorb these vitamins, to clip off these keys from the key chain and the core is K3. Some of it you will find in the blood as K1, MK4, MK7, but some of it you will find K3 in the blood and in the urine.
So we know after taking these vitamins, they measured urinary levels of K3. We know that this is what is happening during metabolism. This K3 goes into all the tissues in the body and then the body seems to prefer to make MK4. 90%. But some of it stays at as K1 or some MK4 stays unchanged. It’s very complex. And then your gut bacteria makes all these different Mks. So it’s very important to consider the bottom line, the clinical effects. We may not know all the conversions. And again, looking at plasma levels is not important because it’s not indicative of the effects. But what is important is to look at the clinical effects, long-term effects in bone density, bone elasticity, if we can measure it. We can look at arterial stiffness. There are some office level tests for arterial stiffness.
Dr. Weitz: You know what’d be interesting, there’s a test that’s done through serum called the pulse test that looks at a bunch of markers that correlates with plaque stability. It’d be interesting to see if patients who took vitamin K had a better score on that test, indicating less unstable plaque.
Cristiana: Yeah, it’d be interesting to see those. I think that arteriosil and tocotrienol has a good chance of showing great effects on those types of tests. But I don’t doubt that having adequate levels of vitamin K in the body through its anti-inflammatory effect. And we know that inflammation is so core to so many detrimental effects that happen, osteoporosis and cardiovascular disease.
Dr. Weitz: And potentially vitamin K could be beneficial for osteoarthritis as well, especially since it plays a role in collagen.
Cristiana: Yes. And the osteoarthritis involves the bone part next to the joint, and then you have the collagen is the tissue, the connective tissue, whether it’s cartilage, whether we have tendons and ligaments that are starting to get frayed. It’s very likely that we don’t have human studies right now, but some studies suggest that. And again, inflammation controlling with omega 3s, huge problem with the US intake of omega 3s, especially the preformed EPA and DHA. I always recommend that test the EPA, AA ratios, the amount of individually looking at EPA and DHA, not just some of them. Because they seem to have different effects on inflammation, and also brain. So yes, I think vitamin K is very exciting to optimize overall body function. Unfortunately, RDA is stuck at that 90-120 micrograms just for clotting. And by the way, taking more vitamin K1 is not going to increase your clotting. It just saturates the ability to support normal clotting. When you take a thousand micrograms of K1 versus a hundred, right, you’re not going to clot any more efficiently. The particular situations where people need anti-clotting medications are very separate than supporting a healthy state.
Dr. Weitz: What do we know about vitamin K and cancer?
Cristiana: Yeah, that’s a very interesting topic and I think it has to do again with the effect on that [inaudible 00:57:35 medalanite] pathway. The Japanese have noticed that they gave for 20, 30 years, the 45 milligrams of MK4 for osteoporosis. They’ve noticed that those women that had hepatitis C virus did not develop liver cancer. That was an interesting side benefit. So why do we think that is? Again, it’s something to do with inflammation and that pathway that produces cholesterol, coQ10 and all those things.
Some people tried intravenous vitamin K3, probably to cause oxidative stress for the cancer. Those are experimental things that are very hard to test. Do we think that it will help in general with cancer risk? Possibly. They tried also vitamin K1 at 40 milligrams I believe. I don’t know that that’s your main approach to reduce cancer risk and treat cancer. It’s interesting to know that K3 is given to animals as a source of vitamin K, a very cheap source of vitamin K. Because their bodies are converting obviously K3 to MK4, just to give them enough to support clotting. They’re not supporting their health because they don’t live long enough to worry about long-term diseases. But yeah, K3 is not accepted as a human supplement.
Dr. Weitz: And you mentioned something to me before we went on air that there may be a role in vitamin K in reducing calcification of the lungs.
Cristiana: Yeah, so during covid, obviously we became aware of vitamin D status being very important and they saw that people with low vitamin D status had higher mortality when hospitalized and so on. And then they started testing vitamin K status through MGP. The un-carboxylated MGP, which we use for arterial calcification. But let’s keep in mind that the lungs actually are an elastic structure. Collagen and elastin. And they hypothesize that if you have adequate vitamin K, you’re not going to have as much calcification. Just like with the arteries, you’re going to have more elastic lungs, which obviously it’s a critical feature when you’re fighting covid, when you have fighting that inflammation during covid exacerbation. So it’s an interesting correlation there. And again, the question is, what is your best supplement to improve vitamin K status? I think K1 at one milligram, at least one milligram. Add in some MK4 in case people are on statins and add GG. Because we want to make sure that that conversion occurs between K1 and MK4, wherever the body wants to do it. Each tissue has its own preference. But yeah, the story from vitamin D optimization has to be changed to vitamin D plus vitamin K optimization. It’s just that the tests for vitamin K status are not as well known and as well used and not as affordable.
Dr. Weitz: Right. Okay. I think those are pretty much the points that I wanted to discuss. I think one more thing, a minor point, but you mentioned to me in one of our discussions that infants are given an injection of vitamin K, and if the mother has adequate vitamin K status, then there’s really no reason for this.
Cristiana: Yeah, I mean, I’m afraid to go against the medical advice.
Dr. Weitz: Right, right.
Cristiana: Even for a friend.
Dr. Weitz: No, nobody should take anything they hear in this podcast as medical advice. You should check with your doctor, et cetera, et cetera.
Cristiana: What I say is this. Again, average intake in US of K1 is 92 milligrams, but then we have a reference range of 30 to 220. So half the population doesn’t get enough vitamin K for clotting for the mother’s body. If you have an infant to support, then you probably need more vitamin K to make sure that the fetus has enough vitamin K, right? So if the mother’s deficient, you’re not going to get probably sufficient vitamin K in the fetal tissues. So I hypothesize that if a mother takes at least two to 300 or one milligram of K1. Let’s say she has a great diet of greens and so on. In Europe, the highest intake is 991 micrograms. So it’s possible from a diet high in fruits and vegetables, or you take the supplement, to have a good status. So the likelihood for the fetus is much lower to have issues with clotting.
Then breastfeeding starts. They have found that MK4 is the dominant form of vitamin K in the milk. Nature puts out these vitamins in the milk for a reason. And I’m pretty sure that a deficient mother, a mother that is deficient in intake of vitamin K1 and/or K2, or if she’s on a statin, she can’t convert to MK4 very well, it’s likely that her infant would be deficient. So that’s kind of what I’m hypothesizing. Each patient has to talk to their doctor and figure out. I think there are tests that they can do on the infant. They don’t want to maybe spend the money, but you can test clotting ability in an infant and the lab is right there. You can do it probably pretty fast to see, does this infant really need this injection? That’s what I’m fantasizing about, but I don’t know what they’re doing in the…
Dr. Weitz: It’s probably cheaper to just give them the injection than to do the test.
Cristiana: Yeah, it’s unfortunate. But yeah, well, tests are so important and are evolving and we have to advocate for them and that’s how…
Dr. Weitz: That’s a big part of functional medicine. As many of us say, test, don’t guess. So to kind of sum up this sum up part of the important points of this discussion. As far as vitamin K goes, there seems to be some incredible benefits for vitamin K, for bone health, for arterial health, for other benefits in the body. And that consuming lots of green leafy vegetables is super important as a source of vitamin K1. And then as far as supplementation goes, vitamin K1 is probably the most important form to get a really good adequate dosage of which would be at least a thousand micrograms or one milligram and possibly up to five. And then to add some MK4 at probably a similar amount. And that if you take an MK7, there’s nothing wrong with that, but probably not as efficient as taking K1 and MK4. And that adding GG with the vitamin K as well as vitamin D is super important.
Cristiana: Yes, I totally agree with these conclusions and we hope to keep monitoring the research and updating formulas and protocols based on what we learn.
Dr. Weitz: Absolutely. Thank you, Cristiana.
Cristiana: You’re welcome. Thank you.
Dr. Weitz: And thank you for making it all the way through this episode of the Rational Wellness Podcast. And for those of you who enjoy listening to the Rational Wellness Podcast, I would certainly appreciate it if you could go to Apple Podcast or Spotify and give us a five star ratings and review. That way more people will be able to discover the Rational Wellness Podcast. And I wanted to say thank you to all the patients that we’ve been working with at our Weitz Sports Chiropractic and Nutrition clinic who, many of whom, most of whom we’ve been able to help with a range of various health conditions from various types of gut disorders to thyroid and hormonal issues, autoimmune diseases and various other cardiometabolic conditions. And so I very much appreciate you and I’m excited about going forwards, helping you to improve your health on your journey towards optimal health. And I wanted to let everybody know that I do have a few openings now for new clients, and you can take advantage of that by calling my White Sports Chiropractic and Nutrition Santa Monica office at 310-395-3111. And we can set you up for a new consultation for functional medicine nutrition, and we can get that going as early as the new year. So give us a call and I’ll talk to you next week.
My husband has a huge jaw cyst that has eaten away his jaw bones. He will need a drain for a year to decompress the cyst and hopefully regrow the bone before surgery to remove it. Because of its bone destruction I was researching ways to help regrow bone and found this video. I purchased designs for health D supreme that has D3/K1/K2/GG. Is this adequate K since he is a 42 year old male or should he take the osteoporosis protocol? Thank you!
I would add the TriK plus Calcium/Magnesium 2:1 400 mg twice per day with meals plus Strontium Citrate 227 mg 2 caps at night plus boron 5 mg plus add powdered collagen plus follow an alkaline diet.