Posts Tagged ‘homocysteine’

In a previous article, I wrote about the importance of protein and how much one should consume on a daily basis. Now I’m going to be a bit more specific.

The most abundant protein in the body is collagen. Also, collagen makes up about ninety-percent of connective tissue. This is important for a number of reasons, not the least, musculoskeletal health. If “musculoskeletal health” seems vague, think: degenerative joint disease, degenerative (spinal) disc disease, disc herniations (or “slipped” discs), tendonitis/osis, osteoporosis, sprains and strains, etc.. Collagen essentially provides the tensile strength of tissues. If you don’t have enough collagen or your collagen is “weak” or poorly formed, you’ll be susceptible to injuries and all types of musculoskeletal disorders; among other problems that I’ll touch on briefly as well.

There are twenty-nine types of collagen throughout the human body. Collagen is a major component in many tissues, especially bone, cartilage (including intervertebral discs), tendons, ligaments, muscles, skin, blood vessels, lung tissue, and even the cornea of the eye. Now you can see how the integrity of your collagen is so vital to the functioning of your body. Remember, structure determines function, and collagen is a major part of your structure. So now let’s discuss how to make and maintain strong collagen.

First, you need (to digest and absorb) adequate amounts of protein in order to supply the raw materials. Remember, the building blocks of protein are amino acids. Any amino acids can be used in some areas on the collagen molecule, but the key ones are proline, lysine, and glycine. You shouldn’t have to be concerned with eating large quantities of food that contain these specific amino acids in high levels. Focus on getting an adequate amount of protein from a variety of sources and that should cover your bases. Although, vegetarians and vegans may want to seek out foods high in these amino acids to be sure. And, those with injuries and/or chronic musculoskeletal conditions may want to ensure higher than typical amounts of these amino acids.

Now I’ll discuss the synthesis of collagen. First, in order for your DNA to begin the process (I’ll keep it simple), you need zinc. There is an important zinc-dependent enzyme, DNA polymerase, that allows for the proper function of DNA. This is why zinc is an extremely important mineral in general. The proper function of DNA is an absolute necessity for every cell in your body; especially cell growth.

As mentioned above, the amino acids lysine and proline are necessary. These amino acids then need to be hydroxylated (which means adding an -OH group). For this reaction to occur, you need iron, vitamin C, and alpha-ketoglutarate. Focus on the iron, vitamin C, getting enough protein and you shouldn’t have to worry about the alpha-ketoglutarate (for the most part).

The next step in forming collagen is known as glycosylation (adding glucose basically). This requires available glucose (or galactose) along with vitamin A and manganese. Now don’t go out consuming pure glucose in order make sure this step happens. But do make sure you have good blood sugar metabolism in order to have it available for the cells to use. I have written several articles related to blood sugar. Click here to read my article on “what” to eat, and here to read about “how” to eat.

After glycosylation, pro-collagen is eventually formed which is/are basically chains that are linked with the help of sulfur. So sulfur is essential for collagen formation, but it does have other roles in the body as well. In supplement form, sulfur can be obtained from “MSM” (or methylsulfonylmethane). Additionally, there are “sulfur-amino acids” that can be taken as supplements or gotten from food. These amino acids are cysteine and methionine. Foods that are especially high in sulfur include kale, cabbage, cauliflower, onions, garlic and eggs.

Pro-collagen then requires transport outside of the cells which again requires vitamin A and zinc.

At this point pro-collagen is converted to collagen and then strengthened by cross-linking the fibers (or fibrils) with the help of copper-dependent enzymes. Please note that this enzyme can be inhibited by high levels of the amino acid homocysteine. If you’re not familiar with homocysteine, I have written about it in another article linked here. If homocysteine inhibits this enzyme, the strength of the collagen fibers may be compromised resulting in weak or dysfunctional collagen. This is extremely problematic and may thwart the whole effort. See my article linked above for the “antidotes” to homocysteine. It will “save” more than just your musculoskeletal health.

That essentially covers the formation of collagen. To recap, here is a list of the most important nutrients: protein (esp. the amino acids: proline, lysine, and glycine), zinc, vitamin C, iron, vitamin A, manganese, sulfur, and copper. Don’t forget healthy blood sugar metabolism. And you can also include the nutrients that are necessary to metabolize homocysteine.

Before I finish, I want to touch on another point. Collagen can form adhesions, so to speak. This is the result of excessive cross-linking of collagen. Essentially, when this happens, the fibers don’t glide along one another smoothly. Adhesions can result in decreased range of motion in a joint; and it can be caused by decreased range of motion (usually post-injury or post-surgery). Adhesions in other structures that require collagen (such as blood vessels) may affect their function as well. The key nutrients for preventing this excessive cross-linking (thus aiding in normal cross-linking) are bioflavanoids. In nature, bioflavanoids are found in the white, pithy part of citrus fruits under the rind. They’re also contained in most fruits and vegetables as well as green tea. So in addition to structural treatments designed to increase range of motion, bioflavanoids may be particularly helpful. These can be obtained from supplements as well as food.

I’ll give you an example of how helpful bioflavanoids can be, as well as collagen formation in general. A 42-year-old patient who had undergone a double-mastectomy was referred to me for herniated discs in her neck as well as shoulder and rib pain (in addition to hip and knee pain). I surmised that most of her symptoms were a result of scarring and adhesion formation from the surgery (in addition to a lack of regeneration or degeneration of collagen in her neck/discs, hip and knee). The reason I felt this was because she had never injured any of those areas and there was no history of “overuse” as in repetitive sports. The surgery can be considered an injury, but regardless, she didn’t recover well if pain and decreased range of motion persisted.

I treated her structurally to get her muscles, ligaments, joints, and even skin functioning optimally. In thinking about the nutritional component of her pain and realizing this concept of adhesion formation and collagen; I instructed her to take a bioflavanoid supplement containing dried fruits and vegetables; and she also began juicing fresh fruits and vegetables (even better!). I also had her take a specific mineral related to sulfur metabolism. After about one month of treatment she reported “I feel better”, “I finally feel good”. After about two months, she was doing great and reported a “75%” improvement in her neck, shoulder, and rib pain and was able to walk long distances without pain in her hip or knee. This is a significant improvement, especially after undergoing surgery, in addition to chemotherapy and radiation. I recently saw her after a three-to four-week hiatus and she reported that a fair amount of the pain and discomfort had come back. Sure enough, the holiday season and her busy schedule interfered with her juicing and taking the supplements which allowed the adhesions to reform and decrease her range of motion, while increasing her pain. It may be unfortunate that she’s currently relying on supplements to remain pain-free, but it sure beats pain medication. With more time and consistency, she should be fine on a well-rounded, whole-food diet.

In conclusion, the array of nutrients necessary for collagen formation and maintenance helps explain why a well-rounded diet is so important. And remember, collagen is important for more than your musculoskeltal health. It’s absolutely vital for your (cardio)vascular system. Oh right, and something as simple as anemia (iron or folic acid/B12 deficiency) and hypochlorhydia can (and most certainly will) affect your musculoskeletal and cardiovascular health. You see, it does all fit together if you can find the missing pieces.

Also, remember that skin is dependent on collagen (among other things), and without sufficient amounts, wrinkles will result. I wonder if those collagen injections people get could be used for more than just vanity. And when the visual effects wear off, does the body “steal” it from (say) the lips to put it where it’s more important for survival? I hope so.

Source: http://www.metabolics.com/

Dr. Robert D’Aquila – NYC Chiropractor – Applied Kinesiology

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Let’s talk about two common types of anemia I see in my patients.  They are self explanatory like iron-deficiency anemia.  Megaloblastc anemia refers to a deficiency of folic acid and/or vitamin B12, and pernicious anemia refers to B12-deficiency specifically.

Every single cell in your body requires folic acid and vitamin B12 in order to “mature” and therefore function properly.  All cells start off immature (and large in size) and become smaller when they mature.  Thus, the term “megaloblastic” refers to the fact the cells stay large in size (mega) without these vitamins. “Macrocytic anemia” is also a term for this condition.

In regards to folic acid deficiency, we run in to some of the same situations as in iron-deficiency – when asking the question: Why is their a deficiency?

The answers are either: a) insufficient consumption of foods containing folic acid; b) lack of absorption; c) an inability to convert folic acid to its active form, and d) complications of its utilization from certain drugs.

In regards to answer “a”, you must obviously consume folic acid through the foods you eat. Some of the best foods that contain high amounts of folic acid (or folate as it is referred to when in food) are: lentils, beans peas, broccoli, spinach, collards, okra, asparagus, and citrus fruits.

As far as answer “b”, regarding absorption – this could result from:

1) Your intestinal villi are literally clogged up due to poor food choices, thus not allowing for absorption of folic acid (and most definitely other nutrients as well).  To “fix” this, you would need to change your diet, and probably have to take supplements that would help detoxify the small intestine.  Examples would be a whole food diet and/or fiber (to “scrub” them clean), bentonite clay (to absorb the toxins), and/or mucilaginous herbs that could help “dissolve” out the toxins.

2) Digestive conditions that can compromise the absorption of folic acid (and any nutrients) are: Crohn’s disease, ulcerative colitis, irritable bowel syndrome, leaky gut syndrome, colon cancer, and perhaps others.

Now for answer “c”.  Folic acid (or folate) needs to be converted to 5-methyltetrahydrofolate (5-MTHF) in order to actually perform its necessary functions at the cellular level.  This inability to convert usually results from a genetic defect. If there is a genetic defect, you may have to take a dietary supplement that contains the converted form.

The medications that interfere with folic acid utilization are: anticonvulsants (dilantin, phenytoin, and primidone), metformin (for diabetes), sulfasalizine (for Crohn’s disease and ulcerative colitis), triamterine (a diuretic), and barbituates.

Wait!  A few more things regarding less common causes (that I see) of folic acid deficiency are: alcohol abuse, kidney dialysis, and liver disease.  And as you’ll see below, more is required during pregnancy and lactation to prevent neural tube defects in the fetus; and for the growing baby.

Let’s now discuss vitamin B12 deficiency.  Why would someone be deficient?  The answers here are either: a) insufficient consumption of foods containing vitamin B12; b) failure to properly absorb B12; c) lack of a substance called intrinsic factor in the stomach (related to absorption); and d) inactive or oxidized B12.

Let’s start with answer “a”. Please be aware that B12 is only contained naturally in animal foods!  You can get certainly get it in vegetarian food sources, but that means it has been “fortified”.  Also, even though the algae product known as spirulina lists B12 on the label; apparently it is simply an analogue of B12 and may actually cause you to become even more B12 deficient.  Read this is you are concerned.  Foods high in B12 are basically every animal product known.

Answers “b” and “c” relate to an inability to absorb B12.  One possibility is for the same reasons as folic acid.  See above. Additionally, vitamin B12 requires a substance called intrinsic factor which is produced by (parietal) cells in the stomach, in order for proper absorption.  Stomach tumors, atrophic gastritis, pancreatic enzyme insufficiency, resection of the part of the small intestine that absorbs B12, autoimmunity towards the stomach cells or intrinsic factor itself, and an excess consumption of alcohol may be prevent B12 absorption through intrinsic factor complications.  See a reference here on the above.  “Pernicious anemia” refers to B12-deficiency anemia when the cause is specifically related to atrophic gastritis/destruction of parietal cells or destruction of intrinsic factor (usually from an autoimmune reaction).

Lastly, I’ll talk about “d”.  Vitamin B12 is known as cobalamin.  This is because the mineral cobalt a necessary part of the B12 complex.  B12 needs to be converted to methylcobalamin or hydroxycobalamin to actually get used properly, which depends on genetic factors.  If this conversion does not occur, B12 will be inactive.  Also, a person under oxidative stress (too many free radicals) may cause cobalt to become oxidized and again not allow B12 to work properly.  In this case, it’s possible to have normal B12 levels on blood analysis, but it will be inactive at the cellular level and thus not work. These people will need to decrease their exposure to free radicals; and mostly likely have to supplement with antioxidants and B12 also.

RDA’s for folic acid and B12 are in the following charts provided by the National Institutes of Health:

Folic Acid

Males and Females
1-3 150 N/A N/A
4-8 200 N/A N/A
9-13 300 N/A N/A
14-18 400 600 500
19+ 400 600 500

Vitamin B12

Males and Females
1-3 0.9 N/A N/A
4-8 1.2 N/A N/A
9-13 1.8 N/A N/A
14-18 2.4 2.6 2.8
19 and older 2.4 2.6 2.8

In conclusion, symptoms of folic acid deficiency are as follows: fatigue, diarrhea, loss of appetite, weight loss, weakness, sore tongue, headaches, heart palpitations, irritability, forgetfulness, and high blood levels of homocysteine (to be discussed in another article).

Symptoms of vitamin B12 deficiency are: fatigue, weakness, constipation, loss of appetite, weight loss, numbness and tingling in the hands and feet, difficulty maintaining balance, depression, confusion, dementia, poor memory, and soreness of the mouth or tongue.

Blood tests can be run to determine folic acid and B12 status.  Especially a complete blood count (with “random distribution of weight” or RDW; and “mean corpuscular volume” or MCV) to check for the red blood cells’ size and associated anemias.  A blood test can also confirm a problem with the gene associated with failure to convert folic acid to its active form.

Vitamin B12 can be measured in blood, but remember if your cobalt has been oxidized, it can show normal levels when in fact the B12 isn’t working.  Methylmalonic acid is a good test (and rarely or never run) for B12 status.

And finally, homocysteine levels can spot a folic acid and/or B12 deficiency.  Homocysteine is related to cardiovascular and neurological problems.  Again, I’ll discuss that in another article.

I also use in-office, applied kinesiology muscle tests when I suspect deficiencies in these vitamins. HOWEVER, I still consider it prudent to use blood tests to see exactly what my patient’s levels are.

ANOTHER VITALLY IMPORTANT POINT! The blood lab’s ranges are often too wide to pick up sub-clinical deficiencies in these vitamins, that may still be causing your symptoms. I use narrower functional ranges for myself and my patients.

Proper food choices and quantities and/or supplements can correct deficiencies.  HOWEVER, do not take more than 1,000 micrograms of folic acid without B12.  This is because folic acid supplementation this high can trigger B12 deficiency symptoms.  In particular, it can cause IRREVERSIBLE nerve damage because of B12 deficiency.  Most supplements contain both vitamins together to prevent this. And the only supplements I’ve seen with 1,000 micrograms (and NO B12) in one tablet or capsule are prescription only. Go figure.

Well, that’s a lot to consider for just two vitamins.  But then again, they are obviously extremely important!

Some information in this article was derived from the National Institutes of Health website.

Dr. Robert D’Aquila – NYC Chiropractor – Applied Kinesiology

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