Koncentrated K a Brief Overview:

The Koncentrated K capsule has 25 mg of MK-4, 0.5 mg of MK-7, 5 mg of K1 and 2 mg of Astaxanthin.

Why this combination?  We chose one pill to do it all because the K vitamins are a “team” in the body, especially when it is recognized that the A to D to K ratio (developed and championed by the author) is critical to sustain in your body for 24 hrs per day.  All K vitamins are similar in structure, but differ in the length of the “side chain”.  The longer the side chain, the better effect and efficiency.  Consequently, the long chain menaquinones, especially MK-7, are important as they are nearly completely absorbed and stay in the blood for the longest time, and then remain available for tissues outside the liver, namely bones, arteries and soft tissues (organs).  Research has also found that Mk7, Mk4 and K1 show up in different tissues within the body, making it important that the Koncentrated K capsule offers the most important K vitamins that research has substantiated as vital to body functioning.  When food derived from different forms of phylloquinone and menaquinones were ingested in equal microgram quantities, menaquinones were found to have a concentration 10 times higher than the phylloquinone (Schurgers & Vermeer, 2000).  Research also shows that MK-7 has a dramatically longer half-life relative to vitamin K1, so the Koncentrated K supplement provides a more stable bioavailability of K in your body over a 24 to 72 hour period  (Schurgers et al., 2007).

Here is what the four natural chemicals look like and as you can easily see, they are in an odd way similar.

 Keep it simple  - - - (the kiss principle hard at work)!!!!!!!!

Lets keep K1 simple:  K1 (phylloquinone) is involved in clotting and bone formation.  Basically that is its job.  It has “backup” duties, but clotting is #1.

Lets keep Astaxanthin simple:  this is a natural product and is the pink in pink salmon, or the pink in rainbow trout, or the pink in pink flamingos.  It is also fat soluble, with a chemical structure similar to K.  Astaxanthin is carried on your neutraphils and leukocytes, which are both types of white blood cells.  Astaxanthin, inhibits the production of MMP-2 and MMP-9 which are chemicals produced by those white blood cells and which tend to induce heart disease (they are chemical irritants to an artery).  Thus, Astaxanthin is a potent antioxidant and opponent to those elements which promote atherosclerosis.  And Astaxanthin is far superior to C as an antioxidant per the literature.  (When one looks at vitamin C, this natural chemical appears to be primarily a virus and bacteria “killer” when taken in sufficient amounts, approximately 6 to 20 grams per day).

Lets keep MK-7 simple:  MK-7 is involved with many of the same things as K1 and MK-4 but is unique in that MK-7 “hangs around” your system for 48 to 72 hrs.  Why?   Most likely to cover for the depletion of K1 and MK-4.   A good way to look at MK-7 is that it is the backup to K1 and MK-4,  kind of a ready reserve of “K” just in case the others are depleted.  The body is just amazing as to the backup systems in place.

Lets keep MK-4 simple:  MK-4 is the plough horse of the K vitamins.  This chemical is quickly processed and distributed.  Why?  Most likely because the body is in constant demand for this natural and friendly chemical.  So, what are the implications for this plough horse?  Research from Canada implicates MK-4 in the prevention of Alzheimer’s.  Research from Japan implicates MK-4 as a preventer and reverser of Osteoporosis.  Other research indicated the potential for MK-4 to stop, reverse, and then prevent atherosclerosis.  MK-4 coupled with Vitamin D and Magnesium, are in theory, a potent “cocktail” that speeds bone healing.  Additionally, MK4 is implicated in kidney stone prevention - just to name a few possibilities.  The advances in vitamin K analysis of tissues in the body have implicated MK-4 as having particular physiological importance.  This vitamer (aka, a natural chemical) is not synthesized in significant amounts by bacteria in the gut and its concentration in nutrients is relatively low.  Nonetheless, MK-4 is abundant in tissues such as brain, pancreas, salivary glands, kidney and sternum.  (Thijssen and Drittij-Reijnders, 1994: Davidson et al.  1998: Thijssen et al.  1996).  This MK-4 tissue distribution is quite distinct from that of the chemically similar vitamins such as phylloquinone (K1).  (For example, in rats the tissue concentration ratios of phylloquinone to MK-4 vary from 24:1 in the liver to 0.1:1 in the brain.  (Davidson et al, 1998).

So, there you have it.  The simple “why” behind Koncentrated K.  We encourage you to read the literature contained in this site so as to “get up to speed” with regard to K and how it may impact your life in a positive mode.  Again, each component has a role to play and basically they are good and good for you.

 

Research

Binkley NC, Krueger DC, Engelke JA, Foley AL, Suttie JW.  Vitamin K supplementation reduces serum concentrations of under-gamma-carboxylated osteocalcin in healthy young and elderly adults.  Am J Clin Nutr.  2000;72:1523-8. 

Binkley NC, et al.  A high phylloquinone intake is required to achieve maximal osteocalcin gamma-carboxylation.  American J of Clin Nutr. 2002;76:1055-60. 

Booth SL, Lichtenstein AH, Dallal GE.  Phylloquinone absorption from phylloquinone-fortified oil is greater than from a vegetable in younger and older men and women.  The J of Nutr.  2002;132:2609-12. 

Booth SL.  Dietary phylloquinone depletion and repletion in older women.  The J of Nutr.  2003;133:2565-69. 

Conly J, Stein K.  Reduction of vitamin K2 concentrations in human liver associated with the use of broad spectrum antimicrobials.  Clin Invest Med.  1994 Dec;17(6):531-9.

Cranenburg EC, Vermeer C, Koos R, Boumans ML, Hackeng TM, Bouwman FG, Kwaijtaal M, Brandenburg VM, Ketteler M, Schurgers LJ. The circulating inactive form of Matrix Gla Protein (ucMGP) as a biomarker for cardiovascular calcification.  J Vasc Res.  2008;45(5):427-36.

Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenice, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molbdenum, Nickel, Silicon, Vanadium, and Zinc (2001).  Food and Nutrition Board (FNB), Institute of Medicine (IOM).  As found online Jan 1 2013  http://www.nap.edu/openbook.php?record_id=10026&page=162

Davidson RT, Foley AL, Engelke JA, Suttie JW.  Conversion of dietary phylloquinone to tissue menaquinone-4 in rats is not dependent on gut bacteria.  J Nutr.  1998;128:220-3. 

Fisher L, Byrnes E, and Fisher AA.  Prevalence of vitamin K and vitamin D deficiency in patients with hepatobiliary and pancreatic disorders. Nutr Res. 2009 Sep;29(9):676-83. 2009.

Garber, AK, Binkley NC, Krueger DC, Suttie JW.  Comparison of phylloquinone bioavailability from food sources or a supplement in human subjects. Journal of Nutr.  1999;129:1201–03.

Gijsbers BLMG, Siong K, Vermeer C.  Effect of food composition on vitamin K absorption in human volunteers.  British J of Nutri.  1996;76:223-229. 

Hodges SJ, Akesson K, Vergnaud P, Obrant K, Delmas PD.  Circulating levels of vitamins K1 and K2 decreased in elderly women with hip fracture.  J Bone Min Res 1993;8:1241-45. 

Huyghebaert N, De Beer J, Vervaet C, Remon, JP.  Compounding of vitamin A, D3, E and K3 supplements for cystic fibrosis patients: formulation and stability study. 2007 Oct;32(5):489-96. 

Institute of Medicine at the National Academy of sciences.  Updated 2001.  URL.  http://www.iom.edu/Object.File/Master?54/411/DRIs.Vitamins.pdf.

Jie KS, Hamulyak K, Gijsbers BL, Roumen FJ, Vermeer C.  Serum osteocalcin as a marker for vitamin K-status in pregnant women and their newborn babies.  Thromb Haemost.  1992 Oct 5;68(4):388-91. 

Jie KG, Bots ML, Vermeer C, Witteman JC, Grobbee DE.Vitamin K status and bone mass in women with and without aortic atherosclerosis: a population-based study.  Calcif Tissue Int. 1996 Nov;59(5):352-6

Knapen HM, Jie KS, Hamulyak K, Vermeer C.  Vitamin K-induced changes in markers for osteoblast activity and urinary calcium loss.  Calcif Tissue Int.  1993 Aug;53(2):81-5. 

Kohlmeier M, Salomon A, Saupe J, Shearer MJ.  Transport of vitamin K to bone in humans.  The J of Nutr.  1996;126:1192S-1196.

Kuwabara A, Tanaka K, Tsugawa N et al. High prevalence of vitamin K and D deficiency and decreased BMD in inflammatory bowel disease. Osteoporos Int. 2009 Jun;20(6):935-42. 

Lamon-Fava S, Sadowski J, Davidson K, O’Brien M, McNamara J, Schaefer E.  Plasma lipoproteins as carriers of phylloquinone (vitamin K1) in humans.  Am J Clin Nutr.  1998;67:1226-31. 

Lamson DW, Plaza SM. The anticancer effects of vitamin K.  Altern Med Rev 2003 Aug;8(3):303-18. 

Mager DR, McGee PL, Furuya KN et al.  Prevalence of vitamin K deficiency in children with mild to moderate chronic liver disease.  J Pediatr Gastroenterol Nutr. 2006 Jan;42(1):71-6. 

McCann JC, Ames BN. Vitamin K, an example of triage theory: Is micronutrient inadequacy linked to diseases of aging. Am J Clin Nutr. 2009 Oct;90(4):889-907. 

Plantalech L, Guillaumont M, Vergnaud P, Leclercq M, Delmas PD.  Impairment of gamma carboxylation of circulating osteocalcin (bone gla protein) in elderly women. J Bone Miner Res. 1991;6(11):1211-6.

Sato T, Schurgers LJ, Uenishi K.  Comparison of menaquinone-4 and menaquinone-7 bioavailability in healthy women.  Nutr J.  2012 Nov 12;11:93.

Schoon EJ, Müller CA, Vermeer C, Schurgers LJ, Brummer R-J M, Stockbrügger RW.  Low serum and bone vitamin K status in patients with longstanding Crohn’s disease: Another pathogenetic factor of osteoporosis in Crohn’s disease?  Gut 2001;48:473–77.

Schurgers LJ, Vermeer C.  Determination of phylloquinone and menaquinones in food.  Effect of food matrix on circulating vitamin K concentrations.  Haemostasis. 2000;30:298-307.                                                                                                                                                                

Schurgers LJ, Vermeer C.  Differential lipoprotein transport pathways of K-vitamins in healthy subjects.  Biochimica et Biophysica Acta.  2002;1570:27-32. 

Schurgers LJ, Teunissen KJ, Hamulyak K, Knapen MH, Vik H, Vermeer C.  Vitamin K-containing dietary supplements: Comparison of synthetic vitamin K1 and natto-derived menaquinone-7.  Blood.  2007;109:3279-83.

Shearer MJ, McBurney A, Barkhan P.  Effect of warfarin anticoagulation on vitamin-K 1 metabolism in man.  Br J Haematol. 1973 Apr;24(4):471–79.

Sokoll LJ, et al.  Changes in serum osteocalcin, plasma phylloquinone, and urinary gamma-carboxyglutamic acid in response to altered intakes of dietary phylloquinone in human subjects.  American Journal of Clinical Nutrition.  1997;65:779-784. 

Suttie JW.  Warfarin and vitamin K.  Clin Cardiol.  1990;13:16-18. 

Suttie  JW.  The importance of menaquinones in human nutrition.  Annu Rev Nutr.  1995;15:399-417. 

Thijssen HH, Drittij-Reijnders MJ.  Vitamin K distribution in rate tissues:  Dietary phylloquinone is a source of tissue menaquinone-4.  Br J Nutr.  1994;72:415-25.

Thijssen HHW, Drittij-Reijnders MJ.  Tissue distribution of vitamin K:  Vitamin K distribution in rate tissues:  Phylloquinone is a source of tissue menaqinone-4.  British J of Nutr.  1994 Sept;72 (3):415-25.

Thijssen HHW, Drittij-Reijnders MJ, Fischer MA.  Phylloquinone and menaquinone-4 distribution in rats:  Synthesis rather than uptake determines menaquinone-4 organ concentrations.  J Nutr.  1996;126:537-43. 

Thijssen HHW, Drittij M-J, Vermeer C, Schoffelen E.  Menaquinone-4 in breast milk is derived from dietary phylloquinone.  British Journal of Nutrition.  2002;87:219–26.

Thujssen HHW, Drittij-Reijnders MJ, Fischer MA.  Phylloquinone and menaquinone-4 distribution in rats:  synthesis rather than uptake determines menaquinone-4 organ concentrations.  J Nutr.  1996 Feb;126(2):537-43.   

Uematsu T, et al.  Effect of dietary fat content on oral bioavailability of menatetrenone in humans.  Journal of Pharmaceutical Sciences.  1996;85:1012-16. 

van Summeren M, Braam L, Noirt F, Kuis W, Vermeer C. Pronounced elevation of undercarboxylated osteocalcin in healthy children. Pediatr Res. 2007;61(3):366-70.

Vermeer C, Shearer MJ, Zittermann A, Bolton-Smith C, Szulc P, Hodges S, Walter P, Rambeck W, Stöcklin E, Weber P.  Beyond deficiency: potential benefits of increased intakes of vitamin K for bone and vascular health. Eur J Nutr. 2004 Dec;43(6):325-35. Epub 2004 Feb 5. 

Vermeer C.  Vitamin K: the effect on health beyond coagulation – an overview.  Food Nutr Res.  2012; 56:10.3402

SUPPLEMENT FACTS:

SERVING SIZE:  1 or 2 Capsules Daily with Fatty Foods or Milk
SERVINGS PER CONTAINER:  60
INGREDIENTS	AMOUNT PER SERVING	%RDA
Vitamin K2 (MK-4) (Menaquinone 4)	25 mg	***
Vitamin K1 (Phylloquinone)	5 mg	6,250%
Vitamin K2 (MK-7) (Menaquinone 7)	0.5 mg	***
Astaxanthin (from Haematococcus pluvialis extract)	2 mg	***
*** Daily Value Not Established
May contain: grape seed extract, soy or soy byproducts (natto powder), wheat, plant starches, gelatin, artificial colors, preservatives.

Who should take Koncentrated K?

Cees Vermeer, a leading vitamin K researcher from Maastricht University in the Netherlands has recently laid out this compelling analysis of who should take supplements of vitamin K.  (Vermeer, 2012).

Children.  Osteocalcin is one of the most abundant proteins in the human body, and during growth its synthesis is at least 10-fold higher than after peak bone mass has been reached.  This means that the vitamin K requirement of children is much larger than that of adults (van Summeren, et al, 2007).  Several studies have demonstrated that the vitamin K status of children during growth is extremely poor.

Pregnant women.  Vitamin K is a fat soluble vitamin.  The growing fetus is in need of vitamin K that is extracted from the mother’s blood stream.  It has been demonstrated that, especially during the last trimester of pregnancy, the vitamin K status of the mother decreases and the supplemented vitamin K results in improvement of osteocalcin carboxylation both in the mothers and the new born (Jie, et al., 1992).  Additionally breast milk can be rapidly enriched by increasing the mother’s vitamin K intake (Thijssen, et al. 2002).

Elderly.  It has been reported that osteocalcin carboxylation, as a marker for general vitamin K status, decreases after the age of 50 (Knapen, et al., 1993).  This may be related to less food intake, decreased intestinal absorption, or increased requirement.  Often this also coincides with the onset of age-related phenomena like an increased rate of bone loss and arterial calcification.  If sub-clinical vitamin K-deficiency can be reduced or eliminated as one independent risk factor for illness or disease, than taking a supplement like Koncentrated K may contribute substantially to postponing disease.

People with an identified disease process, such as coronary heart disease, people with liver damage (Mager et al., 2006), people with impaired intestinal absorption such as Crohn’s disease, cystic fibrosis (Huyghebaert et al., 2007), cancer (Lamson et al, 2003), and galactosemia (Schoon et al., 2001) all would benefit from increasing the amount of vitamin K they ingest in order to prevent deficiency (Kuwabara et al., 2009; Fisher et al., 2009).  This product will help prevent many diseases of the body and can be taken daily on a proactive, preventive basis.  It is a very important solution for people like me – the author- who has received a diagnosis of heart disease and who has calcifications in and around the heart and carotid arteries, and for others concerned with osteoporosis, people on dialysis, people prone to kidney stones, and people with broken bones or stress fractures.  (Note, anecdotal evidence points to broken bone healing time is typically cut in half when you take high does of Vitamin K2, plus 1 gram of magnesium (as magnesium) a day and 10,000 iu’s of Vitamin D.)

People on antibiotics.  Receiving treatment with antibiotics can kill the bacteria that produce and/or liberate vitamin K within your gut.  Prolonged use of broad- spectrum antibiotics may decrease vitamin K synthesis by intestinal bacteria.  Antibiotics are generally non-selective, and will kill the intestinal microflora which your body uses to manufacture vitamin K from plants.  This can reduce vitamin K2 (menaquinone) production by more than 70% when compared to those who are not taking antibiotics (Conly, 1994).  Intestinally active antibiotics can severely limit gut synthesis of menaquinones and increase the importance of vitamin K in the diet. 

People on warfarin or vitamin K antagonists (VKA) should not take any vitamin K supplements at any time unless the ingestion is under strict physician supervision.  The exception is if one is taking a dabigatrin derivative and even then your physician must be part of the knowledge loop.  Let’s not do “dumb”.  However, if you are taking warfarin or a derivative, please let your physician know that there is a growing body of research that indicates that supplementing the warfarin with vitamin K can create a more stable environment and can reduce the number of incidents that often happen with folks taking warfarin.

How to ingest

The Koncentrated K pill should be taken with milk or a fatty meal.  If you have difficulties with milk, try almond or coconut milk, butter or whole whipping cream as it makes for a more efficient absorption of the vitamins.  Vitamin K is absorbed in the intestine (Shearer, et al., 1974), and phylloquinone and menaquinones have both shown improved absorption when ingested with fats.  (Gijsbers, et al., 1996; Uematsu, et al.  1996).  Of note, naturally derived vitamin K1, is more poorly absorbed from food and is better absorbed as a supplement (Gijsbers, et al., 1996; Booth, et al.  2002).  It also takes longer for vitamin K1, derived from food to achieve a peak concentration in comparison to taking a supplement.  (Garber, et al 1999).  Additionally it has been discovered that Vitamin D works best in association with Vitamin K, so keep your vitamin D and beta carotene (a carrot a day) levels up and you should be fine.  The liver makes the Vitamin A in ratio to your D and K levels.  Tip:  Do not take Vitamin A.  Just eat a carrot.

How much to take

At a minimum, you should take one pill per day, as this will provide you with the amount of the vitamin Ks that you need to keep your body “running” effectively.  The transport of vitamin K1, phylloquinone, within your body is primarily via tricyglycerol rich lipoproteins, with a minor fraction carried on LDL and HDL (Lamon-Fava et al. 1998.)  Vitamin K2, menaquinones, are also transported via lipoproteins, with LDL and HDL playing a larger role.  (Schurgers & Vermeer, 2001; Kohlmeier et al.  1996).  Booth and colleagues have suggested that the current level of intake of 90 ug/day (micrograms) for women is not enough to ensure complete gamma carboxylation of osteocalcin.  (Booth, et al. 2003).   This corroborates data from more controlled dietary settings, which suggest that changes to the amount of ucOC (uncarboxylated osteocalcin) measured in the blood begins at levels over 100 micrograms of phylloquinone daily (Sokoll, et al.  1997).  Optimal levels of phylloquinone have been suggested to be 1 milligram/day (Binkley et al, 2002), over ten times the recommended adequate intake.

K is transported on the LDL and HDL cholesterol particles = = = imagine that!

By the way, if you are on a statin and take this product one should see one’s LDL and HDL increase.  Not to worry, if one checks one’s particle size, one should see that the size has increased which is a good thing.

Will your blood clot too much?

A common misconception is that high doses of vitamin K will result in overcoagulation (your blood will “gunk up”).  However, the vitamin K-dependent proteins have a limited number of Gla residues of g-carboxylation per molecule, beyond which there can be no further gamma-carboxylation or excessive coagulation.   You cannot take too much vitamin K, and you will never “over-clot” or “gunk up” your blood at any dosage level.  So, don’t worry, be happy and take your vitamin Ks!

Heads Up:  For the real “geekie” folks that are reading this,  Cephalosporins and salicylates may decrease vitamin K recycling by inhibiting vitamin K epoxide reductase.  Further, cholestyramine, cholestipol, orlistat, mineral oil and the fat substitute, olestra, may decrease vitamin K absorption.  (Hendler, et al. 2001)  Simply put, what you eat or ingest can make a big difference in your body to the “negative” side.  So remember:  YOU ARE WHAT YOU ABSORB!!!!!!!!!

Some more K trivia:  Clotting times, as a means of assessing vitamin K status, are neither particularly precise nor sensitive.  (Vitamin K deficiency differentially affects the degree of gamma-carboxylation of each of its dependent proteins, and there are changes in carboxylation long before changes in clotting time become clinically apparent (Hodges et al, 1993; Sokoll et al., 1997).  This means that clotting time is a good first “cut” at assessing K status, but actual K1 levels along with the uncarboxylated osteocalcin test is a far superior way of measuring or determining K status.

Astaxanthin is one of the many cancer-protective carotenoids found in orange and red fruits and vegetables and in dark leafy greens.  It is added to the feed of farmed salmon to make the fish flesh pink or red and occurs naturally in the diets of wild salmon, as well as trout, red sea bream and shrimp.  Some studies have suggested that astaxanthin benefits fish and shellfish in several ways, including protection against oxidation of essential polyunsaturated fatty acids, protection against the effects of ultra violet light, enhanced immune response and improved reproduction.  Some unique aspects of the astaxanthin structure appear to allow it to pass the "blood brain barrier", meaning it can deliver antioxidant activity benefits directly to the brain, eyes and nervous system.

Koncentrated K The Product:

Vitamin K is one of the indispensable vitamins in the human body.  It appears that many people are deficient contributing to a host of medical maladies. This product and the associated web site is an attempt to provide a solution and a resource to that deficiency while increasing the body of knowledge (the why you are doing what you are doing).  The Koncentrated K capsule provides to you a high enough dose of Vitamin K1, MK-4, MK-7, along with Astaxanthin, that would meet the basic K and Anti-Oxidant requirements of your body. Which, by default, leads to the reduction in the potential for host of ailments.

Current daily recommendations for K vitamins are based exclusively on Vitamin K1 and the requirement for proper blood clotting.  RDI or Recommended Daily Intake is the daily intake level of a nutrient that is considered to be sufficient to meet the requirements of 97-98% of healthy individuals in every demographic in the United States.  RDI’s are revised by the Food and Nutrition Board at the FDA (Food and Drug Administration) every five to ten years.  The Food and Nutrition Board, at the Institute of Medicine within the FDA was established in 1940, and “… advises public agencies on implications of nutrition research for food safety, nutritional status and health, food technology and food processing. They identify needed research and interprets research findings in the interest of public welfare” a definition taken from their website.

The current RDI (Recommended Daily Intake) for vitamin K was 80 µg (microgram) and has been recently increased to 120 micrograms for men and 90 micrograms for women.  In Europe the Commission of the European Communities in October of 2008, recommended a daily intake of 75 micrograms of vitamin K.  As we have presented throughout the pages of this website, there is ongoing and accumulating scientific data that indicates that the majority of people are deficient in vitamin K, (Plantalech, et al., 1991; Jie et al., 1996; Binkley et al. 2000; van Summeren, et al., 2007; McCann et al., 2009) and that those deficiencies can be an important variable in significant disease processes such as heart disease, cancer, bone health, and kidney health.  There is much agreement that new, higher recommendations for vitamin K intake should be formulated, as current RDI’s are inadequate for the optimal function of vitamin K-dependent proteins in other tissues like bone and arteries.  Since vitamin K1 has a short half-life time, the recommended doses are insufficient to reach these peripheral tissues as the body, via the liver, is driven to use the K first in the role of a coagulant (so one does not bleed out).  Once that level of bleed protection is attained the body transports the excess to the rest of the body as needed.

In November 2010, the Institute of Medicine at the National Academy of Sciences indicated there is no upper limit that needs to be recommended for either form of vitamin K in November 2010.  They could find no research on vitamin K that identified any concerns for taking high doses of vitamin K1 and K2.  No known toxicity level exists for vitamins K1 or K2, meaning that they are inherently compatible with the human body and its biochemical needs.  Research has demonstrated that in adults who do not take vitamin k supplements, between 20 and 30% of osteocalcin and MGP (vitamin K dependent proteins) are uncarboxylated, and inactive (Sokoll, et al, 1997; Cranenburg et al, 2008).  Only after supplementation with more than 1 mg/day of vitamin K, or 200 UG/day of MK-7, did carboxylation approach completeness. You want to be carboxylated! (Vermeer et al., 2004)