Expert Guide to Aloe Vera Juice Benefits

Historically, there are several names for aloe vera in Africa, where aloe vera is said to have originated.  In the area, aloe vera is known as ?lily of the desert”, the ?plant of immortality?, and the ?medicine plant”.  It is then believed that its name originally came from the Arabic term ?alloeh” which means ?bitter? for aloe vera’s bitter liquid that is particularly located in the leaves.<br /> <div class="separator" style="clear: both; text-align: center;"> <a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhf2-ZCr0c3DVrRARYnJxGNIXLA8fGo7A1cB1-RB_2doSxpN7b2cr-6YaCsXYJgFoZr8Lv03VrIkIvaFO6_aiytlx1y_91Td-GVXlWBs1z5DHHjvqDStLUT6K6wYYTqpvBzOILsGvEwQwTL/s1600/Expert+Guide+to+Aloe+Vera+Juice+Benefits.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="186" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhf2-ZCr0c3DVrRARYnJxGNIXLA8fGo7A1cB1-RB_2doSxpN7b2cr-6YaCsXYJgFoZr8Lv03VrIkIvaFO6_aiytlx1y_91Td-GVXlWBs1z5DHHjvqDStLUT6K6wYYTqpvBzOILsGvEwQwTL/s400/Expert+Guide+to+Aloe+Vera+Juice+Benefits.jpg" width="400" /></a></div> <br /> Aloe vera has 500 species growing in climates in the whole cosmos.  For the ancient Greeks, Arabs, and Spaniards, aloe vera is commonly used throughout the millennia, and the African hunters until now still rub the plant?s gel on their bodies for the purpose of lessening perspiration and their scent.<br /> <br /> The plant is said to be separated into two main products, and these two include the gel and the latex.  In terms of the plant?s gel, it is interesting to know that it is the leaf pulp and is a thin clear jelly-like substance that is specifically taken from the parenchymal tissue that composes up the inner parts of the aloe leaf.  The gel is composed of carbohydrates polymers, like the glucomannans or pectic acid, and other several organic and inorganic compounds.  On the other hand, the aloe vera latex is commonly known as the ?aloe juice? and it is bitter yellow exudates from the pericyclic tubules which are found just beneath the outer skin of the aloe leaves.  It is both the gel and latex that are used by most aloe vera consumers today.<br /> <br /> The aloe vera is believed to have given some health benefits to those who have had applied it.   It is considered by some researches that the clear gel has a capability to heal wounds, ulcers, and serious burns by just placing an amount or a protective coating on the affected portions and it speeds up the healing rate.<br /> <br /> The aloe vera plant generally composed 96 percent water and the rest of it is composed of active ingredients which involve essential oil, amino acids, minerals, vitamins, enzymes, and glycoproteins.  Due to its effectiveness in healing wounds, ulcers, and burns, many people used it including the contemporary healers since the 1930s.  In fact, from that time until today, several liquid health treatments coming from aloe vera are made and some of them are blends of aloe juice and other plants and herbs.  The aloe vera juice is beneficial for it calms the digestive tract irritations, like the peptic ulcers and colitis.<br /> <br /> The aloe vera, being a food supplement, is in fact said to assist in blood and lymphatic circulation, kidney, gall bladder functions and it facilitates digestion. And since it has a moisturizing effect on the skin, the plant is a common remedy for sunburn and skin irritation.  So if you want to feel the effect of it, just remove the thin outer skin and process the leaves in a blender, then add 500 units of vitamin C powder to every cup and finally store it in the refrigerator.

Aloe Vera Diet fitmiss fitness classes fitness tips for women Health nutrition vitamin b12 Vitamin Mineral workout yoga Expert Guide to Aloe Vera Juice Benefits

Historically, there are several names for aloe vera in Africa, where aloe vera is said to have originated.  In the area, aloe vera is known ...

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Benefits of eating the whole artichoke leaf - Expert Guide

The Artichoke leaf is such a grand perennial plant that has a variety of important functions.  With its purplish flower head, the artichoke leaf is indigenous to southern part of Europe, northern part of Africa, and the Canary Islands.  Artichoke leaf also made its way to popularity in parts of Rome and Greece, when most of the people there began to cultivate the plant.  And it is now grown commercially in North Africa.<br /> <div class="separator" style="clear: both; text-align: center;"> <a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhJAc7YQQO67FVXy3oTL_cr2Xn9IJa66Dnuv74Nfl952PNL-W5Bz9H4lMj9EhzW22NPer_Cy2xYbwiJOUrT5fZ_XnhGiys-ZiEJZUQQnzp4W4-uWk5ahxYtB7Q9_L6CdNkoTFupyXHgnY46/s1600/Benefits+of+eating+the+whole+artichoke+leaf+-+Expert+Guide.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="266" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhJAc7YQQO67FVXy3oTL_cr2Xn9IJa66Dnuv74Nfl952PNL-W5Bz9H4lMj9EhzW22NPer_Cy2xYbwiJOUrT5fZ_XnhGiys-ZiEJZUQQnzp4W4-uWk5ahxYtB7Q9_L6CdNkoTFupyXHgnY46/s400/Benefits+of+eating+the+whole+artichoke+leaf+-+Expert+Guide.jpg" width="400" /></a></div> <br /> It is the flesh of the spike-tipped petals of the artichoke leaf, which is called “bracts”, as well as the heart of its flower head that are particularly eaten by most Europeans as a delicacy.  But outside from such fact, it is greatly artichoke leaf?s large and lobed leaves and their extracts that are widely applied medicinally.<br /> <br /> Since the early days, most of the traditional healers used and approved the artichoke leaf as a major treatment for digestive upset, poor liver functioning, and a array of other disorders.  The artichoke leaf is then primarily used as a choleretic, which is a substance that fortifies the liver function by means of enhancing the bile production.  It is as well known as diuretic, and this centuries-old reputation largely remains for the reason that artichoke leaf really increases urination.<br /> <br /> The artichoke leaf is widely applied as a form of sweetener as well as favoring agent in some alcoholic drinks.  Its stems, leaves, and roots produce an aromatic and bitter substance which inspires the artichoke leaf?s potential in alcoholic liquors that are intended to enhance a good digestion.  Such extremely bitter properties or taste is thought to rouse the production of digestive juices, which is primarily the foundation to which the traditional aperitif is taken before meals in many countries. <br /> <br /> Other resources and researches about this perennial plant mentioned that the artichoke leaf indeed has great potentials for medicine.  One of the beneficial uses of its supplement appears to have a great impact on the liver.  Particularly, in animals, it is noted that the liquid extracts and the leaves of this plant have shown an ability to protect the liver, and there is a great possibility that it will aid the liver cells to regenerate.<br /> <br /> The artichoke leaf also acquires a certain reputation for being the best solution for digestive and bowel problems, although research for such area is not yet conclusive.  And it also plays a vital role in the process of lowering cholesterol so to help in preventing any disorder.<br /> <br /> Although it is only the flower head of such perennial plant is widely made available, there are still some grocery stores that offer the whole artichoke plant for those who wanted to use it for treatment.  You may also find artichoke leaf in multi-ingredient liver remedies which are also composed of another liver supporting herb known as milk thistle.  And due to its widely known uses, a primary active compound of the artichoke leak which is called ?cynarin? is now provided by some stores in standardized extracts.  And until now there is still no other known drug or nutrient interactions that are greatly related to artichoke leaf.

artichoke leaf Diet fitmiss fitness classes fitness tips for women Health nutrition vitamin b12 Vitamin Mineral workout yoga Benefits of eating the whole artichoke leaf - Expert Guide

The Artichoke leaf is such a grand perennial plant that has a variety of important functions.  With its purplish flower head, the artichoke ...

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Why Do We Need Calcium Plus Vitamin D

Growing up we undoubtedly all have been advised at one time or yet another to drink our milk and to eat low fat dairy items. The cause we were advised this is because our parents and caregivers understood that by consuming calcium rich foods our bodies might significantly benefit and our bones and teeth will be healthy and balanced and strong.<br /> <br /> They were right as it is true calcium bets a crucial function in the development and maintenance of healthy bones and teeth. However, calcium not only assists to keep our bones and teeth strong and healthy and balanced it is a really important and necessary nutrient for the complete body. Calcium also bets a really important part in keeping our heart muscles healthy, it aids to manage and control our heart beat and it aid our nerves operation and helps with many other bodily operations.<br /> Everybody requires calcium in their diets. Children and adolescents want adequate calcium in their diets so they are able to take full benefit of the calcium storage space in their bones. As we age, we have to get adequate nutritional calcium to help us minimize the loss of calcium from our bones since the majority of the body’s calcium, roughly ninety-nine percent, is saved in your bones. We likewise require an adequate volume of calcium in the body due to the fact that the additional one percent is saved in the others of the body and is for all other bodily functions.<br /> <div class="separator" style="clear: both; text-align: center;"> </div> <br /> <div class="separator" style="clear: both; text-align: center;"> <a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjSRntQEBHMrDxI0VoeHBmR2bX-wn8qWN8coKwrfNPqFyPHrWBKxd6GIQ3bn4xK7_OPiX4EF3xY4k-FCXiJe4XxQ4nbLpmxjMrDiVQjaQ_jNmrqUR8COtbADrgtdrssWDQVDN0Hp918m7wa/s1600/Why+Do+We+Need+Calcium+Plus+Vitamin+D.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="243" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjSRntQEBHMrDxI0VoeHBmR2bX-wn8qWN8coKwrfNPqFyPHrWBKxd6GIQ3bn4xK7_OPiX4EF3xY4k-FCXiJe4XxQ4nbLpmxjMrDiVQjaQ_jNmrqUR8COtbADrgtdrssWDQVDN0Hp918m7wa/s400/Why+Do+We+Need+Calcium+Plus+Vitamin+D.jpg" width="400" /></a></div> <br /> <br /> Some really good sources of calcium are low fat dairy products, fruits, and fortified cereals and grains. Nevertheless, due to processing and producing the larger part of the nutrients in the meals we consume are diminished. So, it is sad to say, we truly are not getting as much calcium from our diet as we think we are. It is safe to state that it makes a whole lot of sense to take calcium supplements along with ingesting a healthy and balanced diet to ensure that our bodies get just what it needs.<br /> <br /> Even though health supplements is a good concept you really should recognize that not all calcium supplements are produced equal. One such calcium supplement that is well absorbed by the body and is incredibly beneficially all bodily functions is called coral calcium. However exactly what is Coral Calcium? Simply put, Coral Calcium is just calcium. Nevertheless, coral calcium advantages have an benefit over additional kinds of calcium. Marine coral calcium has a broad selection and superior mix of significant and trace minerals. It includes calcium, this mineral and trace minerals, and the ratios of these minerals match the human body?s proportion flawlessly.<br /> <br /> Some forms of coral calcium supplements are inferior due to the fact that a couple of the other vital nutrients have certainly been lost since they have been baked by the sunlight for thousands of years. Marine grade coral calcium is harvested miles out of seacoast below sea level. All of the necessary minerals are safeguarded by nature and made available by thoroughly removing them from the ocean flooring out of the live reefs as not to interrupt them.

Diet fitmiss fitness classes fitness tips for women Health nutrition vitamin b12 Vitamin Mineral workout yoga Why Do We Need Calcium Plus Vitamin D

Growing up we undoubtedly all have been advised at one time or yet another to drink our milk and to eat low fat dairy items. The cause we we...

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Why They Keep Alternative Medicine Silent

If you will find alternative medicines and also natural treatments that actually deliver the results, why do not we hear more about the subject? I don?t think there are numerous real conspiracies close to, yet this really is one of those areas that make me ponder. The actual movement in between government posts as well as positions within the pharmaceutical businesses is actually well documented.<br /> <div class="separator" style="clear: both; text-align: center;"> <a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgRCsMDPVY9MNqJWOaZ97c1fO2WKCoEvz1ZL942rQiHFxH_E2THCRUtZx2glYzyDpIeqr39E8GHUXMyp48hg87WOX6qYQkOD2x3-lcRb1FxDQTYvcPhFDK0aAwEYTGkG8kMWTIxtt5gQ5D3/s1600/Why+They+Keep+Alternative+Medicine+Silent.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="266" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgRCsMDPVY9MNqJWOaZ97c1fO2WKCoEvz1ZL942rQiHFxH_E2THCRUtZx2glYzyDpIeqr39E8GHUXMyp48hg87WOX6qYQkOD2x3-lcRb1FxDQTYvcPhFDK0aAwEYTGkG8kMWTIxtt5gQ5D3/s400/Why+They+Keep+Alternative+Medicine+Silent.jpg" width="400" /></a></div> <br /> Most of the time, though, there’s merely a conspiracy-of-common-interest that prevents risk-free alternative medicines from arriving at market, or coming from becoming well known. For example, drug organizations do not want competition of safe alternatives to their drugs. In the mean time, it’s politically less dangerous for the FDA to not enable an item, because if they approve something and it causes any problems, they get the fault.<br /> Also, natural products, such as silymarin (Milk Thistle Extract), which is used all over Europe to treat poisonings and to guard the actual liver, tend to be lawful here, but not well-known. This is because, being a natural product, there is no way to patent it.<br /> <br /> A natural item additionally can’t be promoted heavily. Imagine if a big company invested hundreds of thousands to advertise a medicinal herb. Every time they received the public?s interest, all the smaller businesses can undercut them in the particular price, given that they spent absolutely nothing on advertising, and a plant product is normally the same regardless of what the actual name on the label.<br /> <br /> Whenever a plant just isn?t approved being a natural therapy, there aren?t any pharmaceutical drug reps available educating doctors about this (Didn’t you know that is just how physicians keep informed?). Furthermore, even when a physician has find out about a helpful plant, he’s more prone to face a malpractice suit to have an allergic attack to an alternative medicine than from killing someone with a ?standard and accepted? remedy.<br /> Companies deal with exactly the same issues of legal responsibility. Additionally, the businesses are limited with what they can say concerning these kinds of natural products. This is why you are able to look all around the box that some plant medicines come in, as well as never once see a mention of what it’s for. It’s tough to find out about these natural treatments, is it not?<br /> <br /> As for my own method, I love to see that there?s really a few real research in which shows a benefit. Anecdotal proof doesn?t mean much. Folks get better all the time, and credit whatever they happened to be using at that time. Alternatively, if it’s inexpensive as well as secure, like eating blueberries to enhance vision, I’ll try almost anything once.<br /> Do natural treatments operate? Sometimes, I have twice eliminated skin growths from my face that could have even been pre-cancerous. These were there for quite some time, yet it took just weeks to make them disappear using a simple and cheap natural product. I?ve additionally witnessed the quickest healing of a cut (on my foot) that I?ve ever seen, after applying a common plant for it. A few alternative medicines do work.

Diet fitmiss fitness classes fitness tips for women Health nutrition vitamin b12 Vitamin Mineral workout yoga Why They Keep Alternative Medicine Silent

If you will find alternative medicines and also natural treatments that actually deliver the results, why do not we hear more about the subj...

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What Are Antioxidants Meant For In Our Bodies

Did you know that fewer than 50% of adults in North America eat the recommended servings of vegetable and fruit each day, who often leave a nutritional gap.<br /> <br /> Although this group of foods is usually rich in many nutrients including for example antioxidants.<br /> Some of the important nutrients include vitamins, proteins and carbohydrates. However, there are other nutrients that most people assume and do not know about. For example, many people would not know what to say if they were asked, what are antioxidants?<br /> <br /> <div class="separator" style="clear: both; text-align: center;"> <a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj7Z7W1SYZ_PqG75VoYMWfzgulxQ8Yisk3Xc9FtEaK16P-RRfJ6gjO0ALnYegzqeCCym5FpXemNMsv63McgZseVyJx4bVAd46eqgvVf-ov1D9jcJWwXPBPYztLKfwb1XRqk42SXJWf2f9iU/s1600/What+Are+Antioxidants+Meant+For+In+Our+Bodies.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="223" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj7Z7W1SYZ_PqG75VoYMWfzgulxQ8Yisk3Xc9FtEaK16P-RRfJ6gjO0ALnYegzqeCCym5FpXemNMsv63McgZseVyJx4bVAd46eqgvVf-ov1D9jcJWwXPBPYztLKfwb1XRqk42SXJWf2f9iU/s400/What+Are+Antioxidants+Meant+For+In+Our+Bodies.jpg" width="400" /></a></div> <br /> Antioxidants terminate these chain reactions by removing free radical intermediates, and inhibit other oxidation reactions. This is done by them being oxidized themselves, so antioxidants are often reducing agents such as thiols or ascorbic acid for example.<br /> <br /> It is antioxidants which stop such destructive physiological processes. They do this through ending the chain reaction through eliminating the free radicals and stopping any oxidation from occurring. This is possible since they get oxidized in place of other molecules. Thiols and scorbutic acid are a good example.<br /> <br /> There are many foods which are rich in this nutrient. Let’s review a few of these next. Some of them include nuts, beans, grains and seeds. Actually, most plants have this nutrient in abundance. Meat, eggs and dairy products also contain a low concentration because animals rely on plants for their nutrition. Hence their products have similar nutrients. Some other rich sources are mushrooms, almonds, Alaskan king crab and pineapples.

Diet fitmiss fitness classes fitness tips for women Health nutrition vitamin b12 Vitamin Mineral workout yoga What Are Antioxidants Meant For In Our Bodies

Did you know that fewer than 50% of adults in North America eat the recommended servings of vegetable and fruit each day, who often leave a ...

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Best Vitamin Mineral Liquid Supplements

Vitamin K status among children with cystic fibrosis and its relationship to bone mineral density and bone turnover<br /> <br /> Steven P. Conway<br /> <br /> ABBREVIATIONS. BMD, bone mineral density; BMC, bone mineral content; BSAP, bone-specific alkaline phosphatase; CF, cystic fibrosis; Gla-OC, carboxylated osteocalcin; Glu-OC, undercarboxylated osteocalcin; PICP, procollagen I carboxy-terminal propeptide; PIVKA-II, prothrombin produced in vitamin K absence; MAb, monoclonal antibody; OC, osteocalcin; AU, arbitrary unit.<br /> <br /> <div class="separator" style="clear: both; text-align: center;"> <a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjk15u6T8LLABIW6dwlx3Af59t0VHzGv0oDbt6J_KF7W89kbKaafoTjDT2iR6aGEHh2FpPwNHk11M5Ogd6mEzr1tZoXi85Ap1v7w4no-XXO-JdqTIBKMluJiw8hXotwFvgb_jQasJ3iPhPg/s1600/vitamins.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="300" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjk15u6T8LLABIW6dwlx3Af59t0VHzGv0oDbt6J_KF7W89kbKaafoTjDT2iR6aGEHh2FpPwNHk11M5Ogd6mEzr1tZoXi85Ap1v7w4no-XXO-JdqTIBKMluJiw8hXotwFvgb_jQasJ3iPhPg/s400/vitamins.jpg" width="400" /></a></div> <br /> Dietary vitamin K is available mostly in green leafy vegetables and some vegetable oils (eg, soybean, rapeseed, and olive oils), as phylloquinone (vitamin [.1]). (1) Gut bacteria synthesize menaquinones (vitamin [.2]), but it is unclear how much these contribute to overall vitamin K status. (1,2) Members of both series can function as the necessary cofactor for the posttranslational conversion of specific glutamyl residues to [gamma]-carboxyglutamyl residues in vitamin K-dependent proteins, such as prothrombin and osteocalcin (OC). The latter, which is produced by osteoblasts, accounts for 10% to 20% of noncollagenous bone proteins, has a high affinity for hydroxyapatite, and plays a regulatory role in bone formation and mineralization. Circulating OC levels are correlated with bone formation. (3)<br /> <br /> Undercarboxylated vitamin K-dependent proteins are functionally defective, and their measurement in serum offers a sensitive marker of vitamin K function for the tissue in which the protein is synthesized. (4) The level of undercarboxylated prothrombin, ie, prothrombin produced in vitamin K absence (PIVKA-II), is a much more sensitive indicator of suboptimal hepatic stores than is the prothrombin time, which remains unchanged until the prothrombin concentration falls below 50% of normal values. (5)<br /> <br /> The liver is more efficient than bone in using available vitamin K and, in the absence of malabsorption, it is rare for a nutritional vitamin K deficiency to be of sufficient severity to impair blood coagulation. The bone vitamin K-dependent proteins are more vulnerable, and a degree of undercarboxylation of OC is naturally present among healthy people of all age groups. (6-9) The measurement of the fraction of total OC as undercarboxylated OC (Glu-OC) is a sensitive indicator of the vitamin K status of bone. (4,8) It is the first functional marker to respond to vitamin K depletion and the last to respond to repletion. (10)<br /> <br /> Children with cystic fibrosis (CF) are at risk of vitamin K deficiency as a result of fat malabsorption, bowel resection, liver disease, and chronic antibiotic use. Isolated cases of severe bleeding with hypoprothrombinemia in infancy were reported in the early 1970s (11,12) and may still occur when neonates with CF receive only oral vitamin K supplements. (13) Routine vitamin K administration at birth removes this risk. (14) Early studies of vitamin K status among older children and young adults with CF yielded conflicting results, documenting adequate vitamin K levels for most patients (15,16) but also vitamin K-associated coagulopathy (17) and increased PIVKA-II levels. (18) Fifty-six of 128 patients (44%) in those 4 studies (15-18) is were receiving vitamin K supplements. In a review article in 1994, Durie (19) concluded that there had not been adequate evaluation of patients at risk but only "conflicting and incomplete answers." Rashid et al (20) subsequently used a sensitive immunoassay for PIVKA-II to assess vitamin K deficiency among 98 pediatric and adult patients with CF who were not receiving vitamin K supplements. Seventy-eight percent of pancreatic function-insufficient patients and all patients with CF-associated liver disease had increased PIVKA-II levels. Similarly, Wilson et al (21) reported abnormal PIVKA-II levels for 81% of 72 pancreatic function-insufficient patients with a mean age of 15 years.<br /> <br /> A limitation of using PIVKA-II as the only index of vitamin K status (20,21) is that it may not distinguish between impaired carboxylation of prothrombin attributable to nutritional vitamin K deficiency and that attributable to liver dysfunction. (22)<br /> <br /> <br /> The aim of this study was to assess vitamin K status in an unselected population of children with CF and to investigate any relationship between vitamin K and bone mineral status and bone turnover. To the best of our knowledge, this is the largest study to document the prevalence of vitamin K deficiency in CF with a combination of tests, including serum phylloquinone measurements to assess tissue stores and specific and sensitive monoclonal antibody (MAb)-based immunoassays to assess the carboxylation of prothrombin in the liver and of OC in bone.<br /> <br /> <br /> METHODS<br /> <br /> <br /> Patients<br /> <br /> <br /> <br /> Children [greater than or equal to] 5 years of age who were attending the Leeds pediatric CF unit were invited to take part in the study. One hundred six children (52 male) entered the study. The z scores for height, weight, and BMI were derived from the 1990 British reference standards. Fifteen children were receiving oral vitamin K supplementation at a dose of 10 mg/day. In accordance with the policy of the CF unit, all pancreatic function-insufficient patients received supplements of the fat-soluble vitamins A and D, with dosages adjusted according to serum levels. Fasting blood samples were obtained, usually between 8:30 and 9:00 AM.<br /> <br /> <br /> Vitamin K studies, serum and urinary bone turnover marker levels, and serum levels of vitamin A (retinol) and vitamin D (25-hydroxyvitamin D) were obtained for most of the children (Table 1). One hundred six patients underwent dual-energy x-ray absorptiometric studies. Three patients had sufficient pancreatic function, and 52 had CF-associated liver disease, defined by the presence of hepatomegaly, increased serum hepatic enzyme levels, and/or abnormalities of the liver on ultrasound scans.<br /> <br /> <br /> <br /> Assessments of Bone Mineral Density and Bone Turnover<br /> <br /> <br /> Bone mineral density (BMD) and bone mineral content (BMC) were measured at the lumbar spine (L2-L4) (spinal BMD and BMC) and for the total body (total-body BMD and BMC) with a GE Lunar Prodigy densitometer (GE Lunar, Madison, WI). Age-matched z scores for BMD were derived from the reference ranges provided by the manufacturer; analysis was performed with software version . Bone formation and resorption were assessed by measuring plasma bone-specific alkaline phosphatase (BSAP) levels, procollagen I carboxy-terminal propeptide (PICP) levels, and free urinary pyridinoline, deoxypyridinoline, and N-telopeptide levels (second morning void urine sample). Urinary bone turnover marker levels were standardized against urinary creatinine valuses.<br /> <br /> Assessments of Vitamin K Status<br /> <br /> Serum phylloquinone (vitamin [.1]) concentrations were measured with high performance liquid chromatography with post-column reduction and fluorimetric detection, as described previously. (23) This method has a lower limit of quantification of ng/mL. The reference range for healthy normolipemic adults is to ng/mL (median: ng/mL) in the fasting state and to ng/mL (median: ng/mL) in the nonfasting state. We defined a suboptimal vitamin [.1] concentration as [less than or equal to] ng/ m L.<br /> <br /> <br /> Serum PIVKA-II levels were measured with a conformation-specific MAb (designated C4B6) in an enzyme-linked immunosorbent assay format. (24,25) Results are expressed as arbitrary units (AUs) per milliliter because circulating PIVKA-II may represent multiple forms of partially carboxylated prothrombin and neither their relative abundance in plasma nor their relative affinity for the antibody is known. Calibration is therefore made against PIVKA-II species purified from patients treated with oral anticoagulant therapy. With electrophoretic techniques, 1 AU is equivalent to 1 [micro]g of purified PIVKA-II. The minimal limit of detection is ~ AU/mL, and we defined values of [greater than or equal to] AU/mL as indicative of an abnormally increased concentration of PIVKA-II.<br /> <br /> Glu-OC and carboxylated OC (Gla-OC) levels were determined with separate immunoassays, in an enzylne-linked immunosorbent assay format, with Glu-OC and Gla-OC kits from Takara Shuzo (Tokyo, Japan). These assays use different MAbs that recognize fully decarboxylated or carboxylated OC, with little or no cross-reactivity. In line with previous recommendations for assessments of the vitamin K status of bone. (8) the Glu-OC fraction was also expressed as a percentage of total OC. A measure of total OC was evaluated by summing the Glu-OC and Gla-OC fractions.<br /> <br /> Statistical Analyses<br /> <br /> Statistical analyses were preformed with Minitab version (Minitab, State College, PA). Anderson-Darling statistical tests were used to determine whether the data were normally distributed. Because most of the data had a nonparametric distribution, results are given as medians and 95% confidence intervals. All patients with undetectable vitamin K levels were excluded from correlation analyses involving vitamin K. Similarly, patients without increased PIVKA-II levels were excluded from correlation analyses involving PIVKA-II. All other correlation analyses used the full data sets. Correlation analyses were performed with logarithmically transformed values for vitamin K and PIVKA-II levels, because of nonparametric distributions. Comparisons of z score results with zero reference values were performed with the 1-sample test. Spearman's rank correlation coefficients were used to evaluate the possible relationships between various parameters. A P value of <.05 was considered significant. The study was approved by the hospital ethics committee, and informed written parental consent was obtained for all study participants.<br /> <br /> RESULTS<br /> <br /> Patient characteristics and measured parameters are shown in Table 1. Mild growth impairment was observed for the patients with CF. Pulmonary function tests and Shwachman-Kulczycki scores indicated mild/moderate disease severity. Age-matched BMD z scores showed a small but significant reduction at the lumbar spine, which might be a reflection of body size. Although we had no control group of the same age range, the median serum vitamin [.1] concentration of ng/mL for the children with CF was greatly reduced, compared with the median of ~ ng/mL for healthy fasting adults. Fifty-four of the 93 children with vitamin K study results had either undetectable ([less than or equal to] ng/mL) or suboptimal ([less than or equal to] ng/mL) serum vitamin [.1] levels, suggesting low tissue stores (Fig 1). Thirty-nine children, 28 of whom also had low vitamin [.1] levels, had increased PIVKA-II levels (> AU/mL), suggesting a functional abnormality of [gamma]-carboxylation of prothrombin (Fig 2). Sixty-five of the 93 children (70%) therefore showed suboptimal vitamin K status, on the basis of low serum vitamin [.1] levels, increased PIVKA-II levels, or both abnormalities.<br /> <br /> [FIGURES 1-2 OMITTED]<br /> <br /> <br /> Of the 15 children prescribed vitamin K supplements, 4 had increased vitamin K levels (3 with normal and 1 with increased PIVKA-II levels), 2 had normal vitamin K and PIVKA-II levels, 2 had low vitamin K levels (1 with normal and 1 with increased PIVKA-II levels), and 7 had undetectable vitamin K levels (5 with increased and 2 with normal PIVKA-II levels). Poor adherence to therapy was suspected for 5 children, including 4 in the latter group. The median serum vitamin [.1] level for the children who received vitamin K supplements and had detectable levels was ng/mL (range: .68 ng/mL). Analysis of the 78 non-supplement-treated children showed that 48 had suboptimal or undetectable levels of vitamin K and 35 had increased serum PIVKA-II levels; 23 of the latter children also had low serum vitamin K levels.<br /> <br /> Serum vitamin K levels were logarithmically transformed, and weak negative correlations were observed with Glu-OC levels (r = , P = .01) and percentages of Glu-OC (r = , P < .05). No other significant correlations were observed between vitamin K levels and bone turnover markers or bone parameters. Serum PIVKA-II levels were also logarithmically transformed, but no correlation was observed with any of the measured parameters.<br /> <br /> Median levels of Glu-OC and Gla-OC were 43 ng/mL and ng/mL, respectively, whereas the percentage of Glu-OC was 71%. Both total OC (represented by the sum of Glu-OC and Gla-OC fractions) and Glu-OC levels were correlated positively with bone marker levels. The strongest correlation was observed with the bone formation markers BSAP and PICP. The percentage of Glu-OC was correlated with bone formation markers less strongly than Glu-OC levels and was not correlated with bone resorption markers. The only association observed with Gla-OC levels was a weakly significant correlation with the bone resorption marker free deoxypyridinoline/creatinine. No significant correlation was observed between Glu-OC levels, Gla-OC levels, or percentage of Glu-OC and any bone parameters (Table 2).<br /> <br /> <br /> The measured bone parameters spinal BMD, spinal BMC, total-body BMD, and total-body BMC were correlated negatively with both bone formation and resorption markers. Slightly stronger correlations were observed with bone resorption markers. No correlations were observed with vitamin A or vitamin D levels.<br /> <br /> DISCUSSION<br /> <br /> The data show that vitamin K deficiency is common among children with CF. On the basis of well-validated assays of vitamin K status, we found that approximately one third of the children (28 of 92 children) had both low serum vitamin [.1] levels and increased PIVKA-II levels, whereas slightly more than one half (54 of 93 children) had suboptimal serum levels of the vitamin. Little is known about the interrelationship of these 2 markers as vitamin K deficiency progresses, but it is known that a rapid decline in hepatic vitamin [.1] stores among surgical patients is mirrored by rapidly declining serum vitamin [.1] levels. (26) After prolonged depletion, the hepatic stores of vitamin [.1] become insufficient to sustain [gamma]-carboxylation of the vitamin K-dependent coagulation factors, and PIVKA-II is produced and released into the circulation. Among healthy subjects, there is a weak but significant negative association between plasma vitamin [.1] levels and PIVKA-II levels. (27)<br /> <br /> It is more difficult to explain the finding of increased PIVKA-II levels in the presence of normal serum vitamin [.1] levels, which was noted for 13 patients. Apart from the possible influence of recent meals, increased PIVKA-II levels may indicate a degree of hepatocellular injury, which may be mild. (25,28) A lack of exact correlation between serum vitamin [.1] levels and PIVKA-II levels (determined with the same assays) was found recently for ICU patients. (22)<br /> <br /> <br /> There was no direct association between vitamin K levels and bone turnover or bone density. This may reflect several confounding factors, such as the impact of the dietary intake in the previous 24 hours on serum vitamin K levels. Another limitation was the fact that many children (33%) had undetectable circulating vitamin [.1] levels, which reduced the statistical power of finding an association. An intervention study is required to show definitively whether there is a correlation between serum vitamin K levels and bone turnover. Vitamin K levels showed a significant negative correlation with levels of Glu-OC, the precursor and presumed inactive form of OC. The latter was correlated significantly with levels of bone turnover markers, as were levels of total OC (71% of which was in the undercarboxylated form). Increased skeletal turnover is associated with rapid bone loss. (29) Through its role in the carboxylation of OC, vitamin K deficiency in CF may be associated with an uncoupling of the normal balance between bone formation and resorption. Vitamin K supplementation for patients with CF may be necessary to avert CF-associated premature osteopenia and osteoporosis. Vitamin K has an excellent safety profile, with no adverse effects being reported with administration of natural sources of the vitamin.<br /> <br /> The molecular role of OC remains unclear, but studies in non-CF populations have provided evidence that improving the carboxylated fraction of OC has a positive effect on bone health and that vitamin K insufficiency contributes to the development of osteoporosis. (30) Low circulating vitamin levels have been documented among elderly women and men with reduced BMD or acute fractures, compared with control subjects. (31-33) Postmenopausal women showed an inverse relationship between Glu-OC levels and BMD. (34) Circulating levels of Glu-OC were increased significantly and were correlated with the subsequent risk of hip fracture. (35) In this patient group, the Glu-OC level was identified as an independent variable from which BMD could be calculated with an accuracy of >70%. (7) Among patients with longstanding Crohn's disease, vitamin K levels were significantly reduced and Glu-OC levels were high, compared with control subjects. (36) The Glu-OC level was also an independent risk factor for, and showed an inverse correlation with, low BMD at the lumbar spine.<br /> <br /> <br /> Vitamin K supplementation may reduce bone loss. Among postmenopausal women, it increased the fraction of Gla-OC and reduced urinary calcium excretion and urinary markers for bone resorption. (37,38) Other intervention studies showed that vitamin K supplements for a variety of subjects could reduce Glu-OC levels, increase bone formation, (4) and improve bone health (32,39) significantly. Data from animal model systems support the clinical trials showing that vitamin K stimulates bone formation and reduces bone resorption. (4) Moreover, vitamin K may have a synergistic interaction with vitamin D. (40,41)<br /> <br /> <br /> <br /> There is no established dietary reference value for vitamin K in the United Kingdom. Department of Health guidelines (42) suggest that a daily intake of 1 [micro]g/kg body weight is adequate for the coagulation function of vitamin K. Studies suggested that mean dietary intakes of phylloquinone among young and old adults in the United Kingdom were in the range of 65 to 85 [micro]g/day. (43,44) However, a substantial proportion of the United Kingdom population (59% in the study by Thane et al (44)) may have daily phylloquinone intakes below the current guideline of 1 [micro]g/kg body weight. There is now strong evidence that much higher dietary intakes are required for [gamma]-carboxylation of OC synthesized in bone than are required for [gamma]-carboxylation of the coagulation proteins synthesized in the liver. (4,27) A subclinical vitamin K deficiency might have a negative effect on bone health while causing no hemostatic consequences. (6,7) There is no current United Kingdom dietary recommendation for the role of vitamin K in the maintenance of bone health. Perhaps in recognition of the importance of this factor, the Institute of Medicine in the United States increased its recommendations for dietary vitamin K intake by ~50%, to 90 [micro]g/day for female subjects and 120 [micro]g/day for male subjects. (45) Sokoll and Sadowski (27) suggested that the normal adult population requires a daily intake between 100 and 400 [micro]g. A vitamin K intake that allows the vitamin K-dependent bone proteins to be in their maximal carboxylated state (6) is probably ~1000 [micro]g/day for healthy adults. (46)<br /> <br /> <br /> Despite the loss of 60% to 70% of the daily dietary intake of phylloquinone through excretion, which emphasizes the need for a continuing daily supply to maintain tissue reserves, (47) vitamin K supplementation is not routine in United Kingdom CF clinics. Patients do receive routine vitamin A, D, and E supplements, however. There has been no consistently recommended level of vitamin K supplementation for patients with CF. The United States consensus statement of 1992 suggested mg weekly for infants, increasing thereafter to 5 mg weekly, (48) a dose that was subsequently shown to be inadequate. (49) More-recent recommendations from the United States, Europe, and the United Kingdom recognized that 5 mg 4 times per week is probably insufficient (50) and recommended a dose range between 1 mg/day and 10 mg/week (51) or 10 mg/day. (52) Authorities stressed the need for additional research before an optimal supplementary dose can be stated confidently.<br /> <br /> This study is limited by the patients' suboptimal vitamin D levels. The CF unit protocol now demands a minimal value of >30 [micro]g/L. Only 13 study patients met this criterion. Twenty-six had levels between 20 and 30 [micro]g/L. High levels of Glu-OC may reflect vitamin D and vitamin K deficiency. (53) Vitamin D and calcium supplements can increase the percentage of Gla-OC among people with low BMD. (39) Uncoupling of the normal balance between bone formation and bone resorption has also been associated with a high vitamin A intake (54) and high serum retinol levels. (55) The median serum vitamin A level of the patient group was at the lower end of the normal range, with no patient showing a high value. Vitamin A imbalance was therefore unlikely to have contributed to any uncoupling of bone formation and resorption. Other potential influences on bone metabolism, including serum proinflammatory cytokine levels, respiratory exacerbation rates, calcium intake, corticosteroid use, activity levels, and general nutritional status, were not analyzed in this study.<br /> <br /> <br /> Another limitation is the lack of comparative data for Glu-OC and Gla-OC levels from a control group of healthy children of the same age range. However, the levels of Glu-OC and Gla-OC in our population were comparable to those observed recently for non-vitamin K-supplemented Dutch CF patients, with the same direct assays. (9) The latter study showed that high-dose vitamin K supplementation ([greater than or equal to] 1 mg/day) decreased and increased the levels of Glu-OC and Gla-OC, respectively, to such a degree that the carboxylation status was improved even beyond that of the healthy control group. Another caveat is that we did not have a validated measure of total OC, although we did use BSAP and PICP and alternative, well-validated markers of bone formation. It was shown that the Takara Glu-OC MAb overestimates the measurement of the amino-terminal-mid-OC fragments and overestimates total OC levels, as represented by the sum of Glu-OC and Gla-OC measurements (. Shearer and C. Gundberg, unpublished data, 2004). As a consequence, the percentage of Glu-OC is also overestimated, compared with its measurement with binding assays. (8) However, studies among elderly subjects showed that the fractional decreases in the percentage of Glu-OC brought about with vitamin K supplementation were very similar whether measured with direct assays for Glu-OC and Gla-OC (as in the present study) or with indirect binding assays (. Shearer and C. Gundberg, unpublished data). These findings justify the use of the MAb-based assays for evaluating the carboxylation status of OC and its response to vitamin K supplementation. Future intervention studies might involve monitoring of vitamin K-induced changes in Glu-OC and Gla-OC levels, bone formation and resorption markers, and BMD.<br /> <br /> CONCLUSIONS<br /> <br /> This study showed that vitamin K deficiency is common among children with CF. Vitamin K levels showed a significant negative correlation with serum Glu-OC levels, which were associated with levels of bone turnover markers, suggesting that vitamin K has a role in maintaining the balance between bone formation and bone resorption. A cause-effect relationship between vitamin K deficiency and low bone mass is not proved. This study did not show any significant correlation between Glu-OC, Gla-OC, or vitamin K levels and any measure of BMD or BMC. Although PIVKA-II concentrations among children with CF have been normalized with vitamin K supplements, changes in the concentrations of bone turnover markers have yielded conflicting results. (9) Vitamin K supplementation among healthy adults may decrease Glu-OC levels without altering N-telopeptide or BSAP levels. (56) These conflicting results probably reflect the multifactorial pathogenesis of CF-related osteoporosis. It is difficult to isolate the discrete contribution to bone health of vitamin K deficiency. The supplemental dose of vitamin K necessary to achieve maximal [gamma]-carboxylation of OC among patients with CF and the effects of these supplements on bone turnover, BMD, and BMC remain to be determined in longitudinal and controlled studies.

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