Vitamin D and Its Importance in Thalassemia

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Offline Andy Battaglia

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Vitamin D and Its Importance in Thalassemia
« on: October 10, 2010, 09:55:07 PM »

This is a full article that suggests a correlation between vitamin D deficiency and heart dysfunction in thal majors. This is a very significant recent study by Dr John Wood, one of the top thal cardiologists on earth. Please refer the doctor to the entire article.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2892922/

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Vitamin D25-OH and D1-25OH levels were compared with cardiac R2[large star] (1/T2[large star]), left ventricular ejection fraction (LVEF), age, ferritin and liver iron in 24 thalassaemia major patients. Vitamin D25-OH levels were reduced in 13/24 patients while vitamin D1-25OH levels were often elevated. Vitamin D25-OH levels decreased with age (r2 = 0·48) and with liver iron (r2 = 0·20). Cardiac R2[large star] was inversely related with the ratio of D25-OH to D1-25OH levels (r2 = 0·42). LVEF was also proportional to the D25-OH/D1-25OH ratio (r2  = 0·49). Vitamin D deficiency may be associated with cardiac iron uptake and ventricular dysfunction in thalassaemia major patients...
These data reinforce prior evidence that serious vitamin D deficiency is common in thalassaemia major patients (Moulas et al, 1997; Napoli et al, 2006). The sharp decline in vitamin D25-OH stores with age probably reflects a combination of decreased intake (dairy products) as well as a shift toward more indoor activities.

We have previously discussed this research at
http://www.thalassemiapatientsandfriends.com/index.php?topic=2909.msg28575#msg28575

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Vitamin D, heart dysfunction tied in thalassemia.
By: Lowry, Fran
Publication: Family Practice News
Date: Saturday, March 1 2008


ATLANTA -- Vitamin D deficiency was strongly associated with high cardiac iron and increased ventricular dysfunction in a retrospective review of 24 young thalassemia major patients.
A review of their medical records showed levels of vitamin D(25[OH]D), the predominant circulating form of vitamin D, were "markedly depressed" in 13 patients and borderline depressed in the remaining patients, said Dr. John C. Wood of Children's Hospital Los Angeles and Keck School of Medicine at the University of Southern California, Los Angeles. There were 11 girls and 13 boys; mean age was 15 years.
Vitamin D(25[OH]D) levels less than 20 ng/mL are considered deficient and D(251OH]D) levels 20-30 ng/mL are borderline or insufficient, Dr. Wood said in a presentation at the annual meeting of the American Society of Hematology. In this study, the mean D(25[OH]D) was 17 ng/mL. The vitamin D levels were then com pared with cardiac R2*--a surrogate MRI measure of the amount of iron in the heart--and left ventricular ejection fraction (LVEF) from each patient's most recent cardiac MRI. As vitamin D levels decreased, cardiac R2* increased. Vitamin D(25[OH]D) levels below 13 ng/mL were associated with severe cardiac iron loading. LVEF also decreased as D25OH decreased.

"In our MRI laboratory, an ejection fraction less than 56% is considered abnormal and indicates poor pump function. In these patients, there was a proportional association between vitamin D(25[OH]D) levels and cardiac function. The four patients with the lowest D(25[OH]D) had an LVEF between 50% and 54%," he said.
The population also was moderately iron overloaded, with mean ferritin levels of 2,089 ng/mL, liver iron 14 mg/g dry weight, transferrin saturation 84%, and cardiac R2* 65 Hz. The normal R2* should not exceed 50 Hz. "Vitamin D deficiency ... is extremely common in thalassemia. Twenty-three of the 24 patients in our study had levels that are considered inadequate to ensure optimal calcium absorption and bone mineralization," he said in an interview. Low vitamin D is linked to decreased cardiac function, muscle weakness, glucose insensitivity, and refractory congestive heart failure.
Increased iron in the heart becomes evident in children with thalassemia major around the age of 9 years. Two-thirds of adults with thalassemia have cardiac iron deposition. Iron cardiomyopathy is the leading cause of death in thalassemia. "Our study describes an association between low vitamin D, high cardiac iron, and increased ventricular dysfunction. We cannot prove [cause and effect], but vitamin D might be worsening the cardiac iron overload and the cardiac dysfunction through its modulation of calcium signaling in these patients."
"Vitamin D deficiency is extremely common in thalassemia, and since osteoporosis is ubiquitous in this disease, vitamin D screening and replacement are probably indicated regardless of the heart findings," Dr. Wood said.

He added that low vitamin D produces secondary hyperparathyroidism, which exacerbates heart failure of any etiology. Because of this, thalassemia patients with ventricular dysfunction should have their vitamin D levels assessed, and replacement should be started if these levels are low.
The National Heart, Lung, and Blood Institute, the Centers for Disease Control and Prevention, and Novartis Pharma funded the study. Dr. Wood disclosed he receives research funding and honoraria from Novartis and Apotex, and is a consultant to Novartis.

Regarding vitamin D and bone mass in thal patients.
http://cat.inist.fr/?aModele=afficheN&cpsidt=17899816

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Low serum levels of 25-hydroxy vitamin D in adults affected by thalassemia major or intermedia
Auteur(s) / Author(s)
NAPOLI N. (1) ; CARMINA Enrico (1) ; BUCCHIERI Salvatore (1) ; SFERRAZZA C. (1) ; RINI G. B. (1) ; DI FEDE G. (1) ;
Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)
(1) Dipartimento di Medicina Clinica e Delle Patologie Emergenti, Via del Vespro 143, 90127 Palermo, ITALIE
Résumé / Abstract
Adult thalassemic patients have reduced bone mass due to disturbances in several different mechanisms affecting bone turnover. To determine if vitamin D deficiency contributes to the low bone mass of adult thalassemic subjects, we studied serum 25-OH-vitamin D levels in 90 patients (age ranging between 21 and 48 years) affected with thalassemia major (TM) and 35 (age 21-56 years) with thalassemia intermedia (TI). TM patients had been receiving regular transfusions from the age of 2 years and had increased serum ferritin, glutamic oxalacetic transaminase, glutamic piruvic transaminase as well as low bone density (L1-L4 Z score -2.07 ± 0.2). TI patients did not receive transfusions, but their ferritin levels were increased as well (520.3 ± 138,1). 8 TM patients (10.1%) and 4 TI (11.4%) had serum 25-OH-vitamin D less than 10.4 ng/ml and were considered presenting an absolute deficiency of vitamin D. Mean 25-OH-vitamin D was significantly (P < 0.01) lower in both TM and TI patients (20.3 ± 0.7 ng/ml and 20.9 ± 2.3 ng/ml, respectively) than in 100 healthy control subjects of similar age (25.2 ± 1 ng/ml). 1,25-OH-vitamin D levels were in the normal-lower levels (45.15 ± 1.5 mg/dl), while 24 H urinary calcium was below the normal range (15.75 mg/dl). In TM patients, the 25-OH-vitamin D levels correlated negatively with age (P < 0.05) and with serum ferritin (P < 0.05). TM and TI patients with low 25-OH-vitamin D levels (<17.8 ng/ml) presented higher serum ferritin levels (P < 0.01) and higher PTH (P < 0.05) compared to those with normal vitamin D. Moreover, TM patients with low 25-OH-vitamin D levels were significantly older (P < 0.05) and had higher GPT (P < 0.05) than patients with normal vitamin D. In conclusion, calcium metabolism is frequently impaired in adult thalassemic patients. An early and effective medical treatment should be taken in consideration by the clinician in order to improve the bone health in these patients.

Please note the dosages used in this study.
http://www.springerlink.com/content/f48h34542203214r/

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Parathyroid and Calcium Status in Patients with Thalassemia

Meenu Goyal, Pankaj Abrol and Harbans Lal

 Abstract
Thirty patients with thalassemia major receiving repeated blood transfusion were studied to see their serum parathyroid hormone (PTH) and calcium status. Serum PTH, serum and 24 h urinary calcium, and serum alkaline phosphatase, phosphorus, and albumin-corrected calcium levels were determined. Half of these patients, in addition to transfusion, were also supplemented with vitamin D (60,000 IU for 10d) and calcium (1500 mg/day for 3 months). Serum PTH, and serum and 24 h urinary calcium concentrations of the patients receiving transfusions were found to be significantly reduced while their serum alkaline phosphatase, phosphorus, and albumin-corrected calcium levels were not significantly altered when compared to the respective mean values for the control group. Vitamin D and calcium supplementation significantly increased their serum PTH and calcium levels. Supplementations also increased urinary excretion of calcium. The results thus suggest that patients with thalassemia have hypoparathyroidism and reduced serum calcium concentrations that in turn were improved with vitamin D and calcium supplementation.

A more general article about calcium and magnesium and the necessary ratio between the two. The two should be taken together along with vitamin D. Calcium taken alone can lead to irregular heartbeats and palpitations. Considering the need for magnesium in thals, calcium should not be considered by itself.
http://www.enerex.ca/articles/calcium_to_magnesium_ratio.htm

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Calcium to Magnesium Ratio

Dr. K. Sharma (Ph.D.)

CAL-MAG

Both calcium and magnesium are involved in numerous metabolic functions and are absolutely essential for the maintenance of a healthy body.

Calcium is considered the backbone mineral because of its role in the formation of skeleton and teeth.  Magnesium is called the natural tranquilizer due to its relaxing action on nerves and muscles.  The biological functions and the therapeutic uses of these minerals are shown below:

FUNCTIONS

CALCIUM
   

MAGNESIUM
       

    * Development and maintenance of bones and teeth (about 99% of body calcium is in bones and teeth)
    * Blood clotting
    * Muscle contraction and relaxation
    * Transmission of nerve impulses
    * Enzyme activation for production of gastric juices
    * Fat, protein and carbohydrate metabolism
    * pH balance
    * etc.

   

    * Development of bones (about 70% of body magnesium is in bones)
    * Crucial part of many enzymes involved in energy production and respiration
    * Transmission of nerve impulses
    * Muscle relaxation
    * Regulation of body temperature
    * pH balance
    * Release of nerve tension
    * Absorption and utilization of calcium, phosphorus, sodium, potassium, vitamins C, E, & D.
    * etc.


THERAPEUTIC USE
 

    * Arthritis, osteoporosis, rheumatism, other bone disorders, dental decay, epilepsy, insomnia, nephritis, pre-menstrual cramps, stress, constipation, muscle pains, high blood cholesterol, regulation of heart beat.

   

    * Arteriosclerosis, heart attacks, Infant death syndrome (SIDS), hypertension, bone fractures, epilepsy, diabetes, alcoholism, kidney stones, leg cramps, nervousness.

Both minerals require each other for their absorption and utilization and must be provided in adequate amounts.  Depending upon the physiological environment, there are cases in which the roles of these two minerals are antagonistic to each other.   Magnesium is located inside the cell (intracellular) while calcium is predominantly located outside the cell (extracellular).  Consequently, the role of magnesium in intracellular metabolic functions, such as energy production, respiration, and muscle contraction-relaxation is antagonistic to calcium.

let us briefly examine the role and relationship of these two minerals in known clinical studies:

REGULATION OF HEART BEAT

The heart is a muscle and its primary function is to pump blood throughout the body.   The heart is composed of billions of cells, each of which works as an electrochemical generator, and contains both calcium and magnesium.  On the outer surface of the heart cells, thin fibers made of a substance called "actin", continually expand and contract in unison with the heartbeat.  The actin fibers are stimulated by calcium, and then relaxed by magnesium.  An electrical charge produced by magnesium then pushes the calcium to the opposite side of the cell.  Thus, calcium helps to produce the heartbeat, and magnesium regulates it.

MYOCARDICAL INFARCTION (Heart Attack)

Several researchers have shown that  a heart failure involves drastic changes in the concentration of cardiac electrolytes (1). During cardiac stress, some of the magnesium is moved out of the cell accompanied by an influx of calcium into the cell.   Thus, the cardiac muscle shows a 20% decrease in magnesium and a 4 1/2 fold increase in myocardial calcium (2).  The loss of magnesium and an influx of calcium seriously disrupts the energy potential of the affected muscle (3).  The situation can be prevented by increasing the level of magnesium.  In clinical practice, intravenous or intramuscular administration of magnesium salts has proven very useful and is highly regarded (4).  It is known that magnesium therapy is the most effective to protect myocardial integrity during cardiac arrest (4,5).  It is interesting to note that in Canadian surveys of post-mortem tissue composition, about 24% less magnesium was found in ischemic hearts than in non-cardiac cases (6).

ATHEROSCLEROSIS (Heart Disease)

A highly dietary intake of magnesium has been attributed to why heart disease is virtually unknown among Bantu tribesman of South Africa while the disease is prevalent among white South Africans.  Clinical studies have revealed that the Bantu's serum magnesium level is about 11% higher than in the white South Africans.  The Bantu's high dietary intake of magnesium is largely attributable to intake of unrefined cereals such as maize meal, which has a high magnesium content and also has a high fiber content (12).  Also, it has been shown that the ability of high-fat diets to induce atherclerosis is prevented by a high magnesium dietary regime (7).

HYPERTENSION (High Blood Pressure)

For many years, hypertension has been associated with sodium.  Consequently, the disorder is treated by substituting potassium in the diet.  However, most of us do not realize that magnesium is also considered a well-known vasodilator.  The anti-hypertensive effect of magnesium is achieved by a direct effect on the vascular wall or is mediated through the central nervous system (8).  Magnesium competes with calcium for binding sites and the net result is that magnesium reduces the calcium-induced contractions.  It is well established that magnesium infusions can cause vasodilation and reduce hypertension in humans (9).

UROLITHIASIS (Kidney Stones)

Canadians appear to have a very high incident of kidney stones and the occurence is particularly high in Newfoundland (11, 12).  In U.S., South Carolina has the highest urolithiasis rate.  South Carolina also has the highest U.S. rate for cardivascular deaths (10).  Both Newfoundland and South Carolina regions have "very soft" drinking waters with little magnesium (11).

In Canada, calcium urolithiasis accounts for 70 to 80% of the total kidney-stone problems (12).  In the U.S., about 67% of all kidney stones are composed of calcium oxalate or calcium hydroxyapatite (11).

Several researchers have used the magnesium/calcium ratio as an index of susceptibility of urine to form kidney-stones in patients (10,13,14).  In general, patients with a urinary magnesium/calcium ratio of 0.7 is normal, whereas a value lower than 0.7 may be considered as stone-forming.  The ratio is especially low in the Canadian "Kidney Stone Patients", indicating inadequate magnesium intake.

The oral magnesium supplementation has proven very effective in the prevention of kidney-stone formation (14).

INFANT DEATH SYNDROME (Sids of Crib Death)

Magnesium deficiency has a primary role in sudden unexpected infant-death syndrome.   The sequence-of-events are as follows:

Magnesium deficiency causes calcium-dependant release of histamine which, in turn, induces increased release of acetylcholine (especially at high calcium/magnesium ratio).   The increased amount of acetylcholine leads to symptoms of neuromuscular hyperirritability and convulsions that can lead to reduced heart rate (15).

The sudden-death syndrome is puzzling since no recognizable allergens are involved.   The symptoms are acute respiratory distress, and includes bronchospasm, shortness of breath, and eventual circulatory collapse.  Hypomagnesemia is observed throughout this syndrome.  Therefore, the role of magnesium in the infant-death syndrome is very significant.

NUTRITIONAL STATUS OF MAGNESIUM

The recommended dietary allowance for magnesium is 300 to 450 mg/day.  There are several factors including pregnancy, rapid growth, or a high intake of protein, vitamin D, calcium, fat, carbohydrates or alcohol, that will increase the requirement for magnesium.

Surveys of dietary magnesium intake from different countries show a prevalence of lower magnesium intake than the desired levels.  In Newfoundland, the intake is only 50% of the recommended amount (16,17).  Other reports (40) show that hospital and institutional diets contain only 61 and 68% of the recommended intake, respectively.   In other studies (18,19), it was found that the intake for pregnant women was only 45 to 60% of the recommended allowances.  There is definite evidence that magnesium intake is suboptimal or marginally inadequate in regions of the Western World (20).   The occurence of hypomagnesemia in humans, due to low magnesium intake and due in part to factors such as, prolonged use of diuretics, alcoholism, pregnancy etc., have been shown to be more prevalent that generally believed (21).

CONTRIBUTION OF DRINKING WATER

Drinking water can significantly contribute to magnesium intake and hard waters can supply 9 to 29% of the daily magnesium intake (23).  Because of the metabolic antagonism between magnesium and calcium, the ratio between these two minerals in the drinking water is of considerable significance.  In a survey of 25 U.S. cities, the lowest death rates from coronary disease were found in areas where the drinking waters supplied more magnesium and less calcium than the U.S. average (24).

Australia has the highest cardiovascular death-rate in the world and also consumes some of the worlds softest drinking waters (60).  On the other hand, the Western region of Texas has the hardest drinking waters and the lowest cardiovascular mortality rates in the United States (25).

The relationship between death-rates from coronary heart disease and the dietary calcium/magnesium ratio in several countries is shown in the following figure:

webgraph.GIF (8793 bytes)

        Relationship between death-rates from coronary heart disease and the average dietary calcium/magnesium ratio in several countries (26).

The high mortality rate in Finland is associated with a high calcium/magnesium ratio (26), while the low mortality rate in Japan is related to a low calcium/magnesium ratio as well as to the "protective" effect conferred by the alkalinity (carbonate-biocarbonate content) of water.

CALCIUM TO MAGNESIUM RATIO

From the information presented here it is apparent that the ratio between calcium to magnesium is very important in dealing with the causes and prevention of a number of disorders including myocardial infraction or arrhythmia, atherosclerosis, hypertension, urolithiasis, and infant-death syndrome.  In all cases, a lower calcium/magnesium ratio or a higher magnesium/calcium ratio is desirable.  This need is further underscored by the fact that magnesium intake is generally suboptimal and that hypomagnesmia is more prevalent than generally believed.

The recommended dietary allowance (RDA) for calcium is 800 mg/day, whereas for magnesium it is 400 to 450 mg/day.  Only about one-third of magnesium is absorbed from dietary sources.  Therefore, a daily magnesium intake of 1200 mg/day has been recommended by some researchers (22).  The traditional ratio of approximately 2 parts calcium to 1 part magnesium needs to be upgraded to increase magnesium intake in view of the overwhelming beneficial role of magnesium.  The ideal ratio for most people's needs is an equal ratio of calcium and magnesium.

The absorption and metabolism of calcium and magnesium is one of mutual dependence, and therefore, the balance between these two minerals is especially important.  If calcium consumption is high, magnesium intake needs to be high also.

VITAMIN D

Vitamin D is necessary to enhance calcium absorption.  Vitamin D works with the parathyroid hormone "PTH" to regulate the amount of calcium in the blood.   It also stimulates the production of a calcium binding protein (CABP) in the intestinal wall which helps absorption.

References

         1. Seelig, M.S.. 1972 Recent Advances in Studies on Cardiac Structure and Metabolism. Vol. 1: Myocardiology. Publ. By University Park Press, London, Baltimore. Pp 615-638
         2. Matyushin, I.F. and Samartseva, T.F. 1972. Kardiologiya 12(3): 1963-69.
         3. Levin, R.M., Haugaard, N. and Hess, M.E. 1969. Biochem. Pharmacol. 25: 1963-69
         4. Petrie, R.H. et al. 1978. Amer. J. Obstetr. Gynecol. 130: 294-299
         5. Hearse, D.J., Stewart, D.A. and Braimbridge, M.V. 1978. J. Thoracic Cardiovasc. Surg. 75: 877-885
         6. Anderson, T.W., et al. 1975. Canada Med. Association J. 113: 199-203
         7. Thrivikraman, K.V. and George, S. 1972. J. Animal Morphol. 19: 196-204.
         8. Szelenyi, I. 1973. World Rev. Nutr. Diet. 17: 189-224.
         9. Singh, R.B. et al. 1976. Acta Cardiol. 31: 401-409 and 221-226.
        10. Mukai, T. and Howard, J.E. 1963. Bull. Johns Hopkins Hosp. 112(5) 279-290.
        11. Churchill, D.N. et al. 1978. Annuals Internal Med 88: 513-514.
        12. Yendt, E.R. and Cohanim, M. 1978. Canada Medical Association. J. 118: 755-758.
        13. Bastian, H.P. and Vahlensieck, W. 1975. Europ. Urol. 1: 235-237.
        14. Gershoff, S.N. and Prien, E.L. 1967. Amer. J. Clin. M. Nutr. 20: 393-399.
        15. Cadell, J.L. 1972. Lancet, Aug 5, pp 258-262
        16. Neri, L.C. and Marier, J.R. 1978. In: Proc Symp June. Bloomington, Minnosota.
        17. Fodor, J.G. Pfiffer, G.J. and Papezik, V.S. 1973. by. Canada Medical Association. J. 108: 1369-1373
        18. Ash, J.R., Schofield, F.A. and Gram, M.R. 1979 J. Clin. Nutr. 32: 286-291.
        19. Seelig, M.S. 1978. Cardiovasc. Med. June. Pp 637-650.
        20. Anderson, T.W. 1977. Nova Scotia Med. Bull. Apr. pp 58-61.
        21. Becking, G.C. and Morrison, A.B. 1970. Biochem. Pharmacol. 19: 2939.
        22. Ashmead, D. Chelated Mineral Nutrition. 1981. Publ. By Institute Publishers, Huntington Beach, Calif pp 162.
        23. Hankin, J.H., Margen, S. and Goldsmith, N.F. 1970. J. Amer. Dite. Assoc. 56: 212-224.
        24. Schroeder, H.A. 1966. J. Amer. Med. Assoc. 195: 81/125-85/129.
        25. Dawson, E.B. et al. 1978. Amer. J. Clin. Nut. 31: 1188-1197.
        26. Karpmannen, H., Pennanen, R. and Passinen, L. 1978. Adv. Cardiol. 25: 9-24

www.Enerex.ca

This post will be also posted as  new thread in the Diet, Nutrition and Supplements board.
Andy

All we are saying is give thals a chance.

 

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