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PubMed1977

Feedback regulation of vitamin D metabolism by 1,25-dihydroxycholecalciferol.

Many factors influence the production of 1,25(OH)2D3 (1,25-dihydroxycholecalciferol) by the kidney. One important factor seems to be feedback regulation by 1,25(OH)2D3 itself. Administration of 1,25(OH)2D3 to vitamin D-deficient chicks abolishes renal 25(OH)D3(25-hydroxycholecalciferol)1-hydroxylase activity and induces the appearance of 25(OH)D3 24-hydroxylase activity. It is likely that these effects are mediated via a nuclear effect, as they are prevented by pretreatment with actinomycin D and alpha-amanitin. Further, 1,25(OH)2D3 has a marked effect on gene transcription in the kidney cell, as assessed by measurement of RNA polymerase activities. RNA polymerase I and II activities are 80-90% inhibited by 12.5nmol of 1,25(OH)2D3 within 30min of subcutaneous administration, indicating an immediate and massive decrease in total gene transcription. By 4h RNA polymerase II activity has returned to control values, but RNA polymerase I activity is markedly enhanced. These results are consistent with the view that regulation of cholecalciferol metabolism in the kidney is associated with an effect of the active metabolite on the kidney nucleus.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1979

Determination of vitamin D and its metabolites in plasma from normal and anephric man.

A multiple assay capable of reliably determining vitamins D(2) and D(3) (ergocalciferol and cholecalciferol), 25(OH)D(2) (25-hydroxyvitamin D(2)) and 25(OH)D(3) (25-hydroxyvitamin D(3)), 24,25(OH)(2)D (24,25-dihydroxyvitamin D), 25,26(OH)(2)D (25,26-dihydroxyvitamin D) and 1,25(OH)(2)D (1,25-dihydroxyvitamin D) in a single 3-5ml sample of human plasma was developed. The procedure involves methanol/methylene chloride extraction of plasma lipids followed by separation of the metabolites and purification from interfering contaminants by batch elution chromatography on Sephadex LH-20 and Lipidex 5000 and by h.p.l.c. (high-pressure liquid chromatography). Vitamins D(2) and D(3) and 25(OH)D(2) and 25(OH)D(3) are quantified by h.p.l.c. by using u.v. detection, comparing their peak heights with those of standards. 24,25(OH)(2)D and 25,26(OH)(2)D are measured by competitive protein-binding assay with diluted plasma from vitamin D-deficient rats. 1,25(OH)(2)D is measured by competitive protein-binding assay with diluted cytosol from vitamin D-deficient chick intestine. Values in normal human plasma samples taken in February are: vitamin D 3.5+/-2.5ng/ml; 25(OH)D 31.6+/-9.3ng/ml; 24,25(OH)(2)D 3.5+/-1.4ng/ml; 25,26(OH)(2)D 0.7+/-0.5ng/ml; 1,25(OH)(2)D 31+/-9pg/ml (means+/-s.d.). Values in two normal human plasma samples taken in February after 1 week of high sun exposure are: vitamin D 27.1+/-7.9ng/ml; 25(OH)D 56.8+/-4.2ng/ml; 24,25(OH)(2)D 4.3+/-1.6ng/ml; 25,26(OH)(2)D 0.5+/-0.2ng/ml. Values in anephric-human plasma are: vitamin D 2.7+/-0.8ng/ml; 25(OH)D 36.4+/-16.5ng/ml; 24,25(OH)(2)D 1.9+/-1.3ng/ml; 25,26(OH)(2)D 0.6+/-0.3ng/ml; 1,25(OH)(2)D was undetectable.

Animals↗
PubMed1979

Effect of vitamin D deficiency on bone formation in the chick.

1. The process of diaphyseal bone formation can be investigated by studying the rate of incorporation of radioactive precursors, administered in vivo into bone fractions of increasing density. 2. In the 4-week-old vitamin D-treated chick most of the osteoid becomes calcified within 12h and almost all within 2 days. The low-density calcified phase that is formed is converted into a higher density form and within 7 days the greater proportion of the calcified tissue is in the higher density form. 3. In the vitamin D-deficient chick of similar age the rate of calcification of osteoid is decreased, as is the rate of conversion into the higher density phase with the resultant accumulation of the lower density calcified form. 4. The higher density phase probably corresponds to hydroxyapatite and the lower density one to the ACP-pase described by Termine & Posner [(1967) Calcif. Tissue Res. 1, 8--23]. 5. The disorder in the process of calcification seems to be unrelated to the alteration in blood Ca2+ and phosphate concentrations, but related to the presence or absence of cholecalciferol.

Animals↗
PubMed1984

Peptide-chain initiation in duodenal mucosa of rachitic chicks after 1 alpha-,25-dihydroxycholecalciferol administration.

The post-ribosomal fraction of chick duodenal mucosa contains Met-tRNAMetf-binding protein(s) that behaves like the eukaryotic initiation factor (eIF-2) in protein synthesis. The binding activity of cytosol protein can be measured by retention of the radioactive complex formed on a nitrocellulose membrane. Complex-formation requires Met-tRNAMetf and GTP or guanosine [beta, gamma-methylene] triphosphate, and is inhibited by aurintricarboxylic acid. The ternary initiation complex thus formed can bind to ribosomal particles from chick intestine. By sucrose-density-gradient centrifugation, [35S]Met-tRNAMetf was found to bind exclusively to 40S and not to 60S ribosomal subunit particles. In the duodenal mucosa of rachitic chicks the ability of the cytosol proteins to promote the binding of Met-tRNAMetf to ribosomal particles via ternary-complex formation is detectably increased by 3 h after injection of 1 alpha,25-dihydroxycholecalciferol, the active form of vitamin D. Cholecalciferol and ergocalciferol under the same experimental conditions failed to stimulate Met-tRNAMetf-binding activity.

Animals↗
PubMed1985

The respiration and calcium content of heart mitochondria from rats with vitamin D-induced cardionecrosis.

Mitochondria were isolated from the heart and skeletal muscle of rats treated with three consecutive daily doses of 100 000 i.u. of calciol (cholecalciferol; 'vitamin D3'). On the fourth day after the last dose, cardiac necrosis developed. At that time mitochondria isolated from heart displayed a 10-fold higher Ca2+ content and a 6-fold lower respiratory rate with pyruvate-plus-malate as substrate as well as with other NAD-dependent substrates. No decrease in respiratory rate with succinate as substrate was observed. EDTA (5 mM) added to the medium during the isolation procedure restored both the high respiratory rate with pyruvate + malate and the low Ca2+ content of the heart mitochondria. The addition of 1 mM-CaCl2 to the medium in which a healthy (control) rat heart had been homogenized caused the same impairment of the mitochondria as did calciol treatment of the animals. No changes of mitochondria isolated from skeletal muscle were observed in rats treated with calciol. It is concluded that the heart mitochondria in vivo fail to accumulate Ca2+ from the cardiac cell overloaded with Ca2+ as the consequence of calciol treatment. Mitochondrial Ca2+ accumulation occurs during the isolation procedure unless an appropriate amount of chelating agent is added to the homogenization medium. The implication of these findings for the biochemical sequence of events in the calciol-induced cardiac necrosis is discussed.

Animals↗
PubMed1988

Presence of sterol-binding sites in the cytosol of French-bean (Phaseolus vulgaris) roots.

Vitamin D3 (cholecalciferol) and stigmasterol have been shown to stimulate Ca2+ uptake and to induce calmodulin synthesis in cultured French-bean (Phaseolus vulgaris) roots. In addition, the appearance of calmodulin in the cultures in response to vitamin D3 could be prevented by RNA-synthesis inhibitors. To investigate the possibility that the sterols affect root DNA transcription through a receptor-mediated mechanism, the existence of sterol-binding sites in P. vulgaris roots was investigated. Specific binding of [3H]vitamin D3 could be demonstrated with intact tissue and the cytosolic fraction obtained therefrom. Equilibrium in the binding reaction with cytosol was attained after 4 h of incubation at 0 degrees C. The [3H]vitamin D3 was reversibly bound, since it could be displaced by an excess of unlabelled sterol. An equilibrium binding constant (KD) of (3.48 +/- 0.09) x 10(-9) M and a maximum binding-site concentration (nmax) of 32 +/- 2.54 (3) pmol/mg of protein could be calculated by Scatchard [(1949) Ann. N.Y. Acad. Sci. 51, 660-672] analysis. In addition to vitamin D3, stigmasterol and sitosterol were effectively able to compete with [3H]vitamin D3 for binding to root cytosol. Cortisol, oestradiol and progesterone displaced bound labelled vitamin D3 to a lesser extent, whereas 5 beta-dihydrotestosterone, lanosterol and diosgenin were ineffective. The affinity and specificity of the root sterol-binding sites are in agreement with the characteristics of tissue responses to the sterols (Ca2+ uptake and calmodulin synthesis).

Binding Sites↗
PubMed1978

The absence of 24,25-dihydroxycholecalciferol in anephric patients.

1. In subjects with normal renal function there was a strong positive correlation between serum concentrations of 25-hydroxycholecalciferol and 24,25-dihydroxycholecalciferol, as measured by competitive protein-binding assay. 2. The 24,25-dihydroxycholecalciferol concentration was about 7% of the prevailing 25-hydroxycholecalciferol concentration. 3. In contrast, sera from anephric patients contained very low or undetectable amounts of 24,25-dihydroxycholecalciferol even after the serum 25-hydroxycholecalciferol concentrations in these patients had been elevated by oral administration of 25-hydroxycholecalciferol. 4. In a further group of anephric patients, all having normal serum 25-hydroxycholecalciferol concentrations, no radioactively labelled 24,25-dihydroxycholecalciferol was formed from an injected pulse dose of [3H,14C]cholecalciferol. 5. These results indicate that in man the kidney is the major site of 24-hydroxylation of 25-hydroxycholecalciferol.

Adult↗
PubMed2002

[Treatment of a solitary adenoma of the parathyroid gland with ultrasound-guided percutaneous Radio-Frequency-Tissue-Ablation (RFTA)].

Radio-Frequency-Tissue-Ablation (RFTA) for the treatment of primary and secondary tumours of the liver has been used for several years, but this minimally invasive treatment is not limited to the liver. A patient suffering from symptomatic postmenopausal osteoporosis, additionally having primary hyperparathyroidism since 1995, refused a surgical resection of the adenoma of the parathyroid gland. Sonographically a 16 mm hypoechoic tumour dorsal of the right upper pole of the thyroid gland was detected. Osteodensitometry: severe osteoporosis of the lumbar spine (88 % of the norm for this age group). Blood check: Elevation of serum calcium level (3.1mmol/l) and serum parathormone level 274 pg/dl (N: 10-50). A percutaneous ultrasound guided RFTA of the adenoma of the thyroid gland was carried out. After RFTA the serum parathormone levels and the serum calcium levels dropped back to normal. The patient was followed-up for one year. For the first time a sufficient therapy for osteoporosis comprising calcium, etidronate and cholecalciferol could be carried out. The osteodensitometry carried out one year after treatment showed an increase in bone density. For the treatment of symptomatic primary hyperparathyroidism RFTA can be a therapeutic alternative for patients with contraindications for surgery.

Adenoma↗
PubMed2002

[The "needle man": more than 40,000 injections in 40 years].

HISTORY AND ADMISSION FINDINGS: A now 65-year-old man had undergone a subtotal thyroidectomy over 40 years ago, which postoperatively resulted in hypoparathyroidism. His doctor began daily intravenous injections of a calcium preparation (1880 mg to 3760 mg calcium per day, over 40000 injections during this period), a regimen continued subsequently by a total of more than 15 other doctors for over 40 years. On admission the patient complained of oral paresthesias and paresthesias of the limbs. INVESTIGATIONS: Low calcium and parathormone levels confirmed the diagnosis of hypoparathyroidism. TREATMENT AND COURSE: Normal levels of calcium were achieved after a short course of 1.25-dihydroxycalciferol. This was followed by the administration of cholecalciferol and calcium. The patient soon became symptom-free and calcium levels returned to normal. Late sequelae have been calcification of the basal ganglia, first signs of nephrocalcinosis and bilateral cataract. CONCLUSION: This case demonstrates that appropriate treatment of hypoparathyroidism [corrected] might not be given in every case.

Aged↗
PubMed1992

Hypervitaminosis D associated with drinking milk.

BACKGROUND: Vitamin D has been added to milk in the United States since the 1930s to prevent rickets. We report the unusual occurrence of eight cases of vitamin D intoxication that appear to have been caused by excessive vitamin D fortification of dairy milk. METHODS: Medical records were reviewed and a dietary questionnaire was sent to eight patients who had unexplained hypervitaminosis D. Vitamin D analyses with high-performance liquid chromatography were performed on samples of the patients' serum, the dairy milk they drank, and the vitamin D concentrate added to the milk. RESULTS: All eight patients drank milk produced by a local dairy in amounts ranging from 1/2 to 3 cups (118 to 710 ml) daily. All had elevated serum 25-hydroxyvitamin D concentrations (mean [+/- SD], 731 +/- 434 nmol per liter [293 +/- 174 ng per milliliter]). Six of the eight patients had elevated serum vitamin D3 concentrations. Of the eight patients, seven had hypercalcemia and one had hypercalciuria but normocalcemia (mean serum calcium, 3.14 +/- 0.51 mmol per liter [12.6 +/- 2.1 mg per deciliter]). Analysis of the dairy's vitamin D-fortified milk revealed concentrations of vitamin D3 (cholecalciferol) that ranged from undetectable to as high as 232,565 IU per quart (245,840 IU per liter). An analysis of the concentrate that was used to fortify the milk, labeled as containing vitamin D2 (ergocalciferol), revealed that it contained vitamin D3. CONCLUSIONS: Hypervitaminosis D may result from drinking milk that is incorrectly and excessively fortified with vitamin D. Milk that is fortified with vitamin D must be carefully monitored.

Adult↗
PubMed1992

The vitamin D content of fortified milk and infant formula.

BACKGROUND: The fortification of milk and infant formula with vitamin D has had an important role in eliminating rickets in children and osteomalacia in adults. A recent outbreak of vitamin D intoxication caused by drinking milk fortified with excess vitamin D has led to questions about the level of vitamin D in milk from other producers. METHODS: We used high-performance liquid chromatography to measure vitamin D in samples of 13 brands of milk with various fat contents and 5 brands of infant formula purchased at random from local supermarkets in five Eastern states. RESULTS: Only 12 (29 percent) of the 42 samples of the 13 brands of milk and none of the 10 samples of the 5 brands of infant formula contained 80 to 120 percent of the amount of vitamin D stated on the label. Twenty-six of the 42 milk samples (62 percent) contained less than 80 percent of the amount claimed on the label. No vitamin D was detected in 3 of the 14 samples of skim milk tested (lower limit of assay, 4.7 IU per quart [5.0 IU per liter]). One milk sample labeled as containing vitamin D2 (ergocalciferol) contained vitamin D3 (cholecalciferol). Seven of the 10 samples of infant formula contained more than 200 percent of the amount stated on the label; the sample with the highest concentration contained 419 percent of the stated amount. None of the samples of infant formula contained less than the amount stated. CONCLUSIONS: Milk and infant-formula preparations rarely contain the amount of vitamin D stated on the label and may be either underfortified or overfortified. Since both underfortification and overfortification are hazardous, better monitoring of the fortification process is needed.

Animals↗
PubMed1992

Vitamin D3 and calcium to prevent hip fractures in elderly women.

BACKGROUND: Hypovitaminosis D and a low calcium intake contribute to increased parathyroid function in elderly persons. Calcium and vitamin D supplements reduce this secondary hyperparathyroidism, but whether such supplements reduce the risk of hip fractures among elderly people is not known. METHODS: We studied the effects of supplementation with vitamin D3 (cholecalciferol) and calcium on the frequency of hip fractures and other nonvertebral fractures, identified radiologically, in 3270 healthy ambulatory women (mean [+/- SD] age, 84 +/- 6 years). Each day for 18 months, 1634 women received tricalcium phosphate (containing 1.2 g of elemental calcium) and 20 micrograms (800 IU) of vitamin D3, and 1636 women received a double placebo. We measured serial serum parathyroid hormone and 25-hydroxyvitamin D (25(OH)D) concentrations in 142 women and determined the femoral bone mineral density at base line and after 18 months in 56 women. RESULTS: Among the women who completed the 18-month study, the number of hip fractures was 43 percent lower (P = 0.043) and the total number of nonvertebral fractures was 32 percent lower (P = 0.015) among the women treated with vitamin D3 and calcium than among those who received placebo. The results of analyses according to active treatment and according to intention to treat were similar. In the vitamin D3-calcium group, the mean serum parathyroid hormone concentration had decreased by 44 percent from the base-line value at 18 months (P < 0.001) and the serum 25(OH)D concentration had increased by 162 percent over the base-line value (P < 0.001). The bone density of the proximal femur increased 2.7 percent in the vitamin D3-calcium group and decreased 4.6 percent in the placebo group (P < 0.001). CONCLUSIONS: Supplementation with vitamin D3 and calcium reduces the risk of hip fractures and other nonvertebral fractures among elderly women.

Aged↗
PubMed2003

A pathway for the metabolism of vitamin D3: unique hydroxylated metabolites formed during catalysis with cytochrome P450scc (CYP11A1).

Metabolites of vitamin D3 (D3) (cholecalciferol) are recognized as enzymatically formed chemicals in humans that can influence a wide variety of reactions that regulate a large number of cellular functions. The metabolism of D3 has been extensively studied, and a role for three different mitochondrial cytochrome P450s (CYP24A, CYP27A, and CYP27B1) has been described that catalyze the formation of the 24(OH), 25(OH), and 1(OH) metabolites of D3, respectively. The hormone 1,25-dihydroxyvitamin D3 has been most extensively studied and is widely recognized as a regulator of calcium and phosphorous metabolism. Hydroxylated metabolites of D3 interact with the nuclear receptor and thereby influence growth, cellular differentiation, and proliferation. In this article, we describe in vitro experiments using purified mitochondrial cytochrome P450scc (CYP11A1) reconstituted with the iron-sulfer protein, adrenodoxin, and the flavoprotein, adrenodoxin reductase, and show the NADPH and time-dependent formation of two major metabolites of D3 (i.e., 20-hydroxyvitamin D3 and 20,22-dihydroxyvitamin D3) plus two unknown minor metabolites. In addition, we describe the metabolism of 7-dehydrocholesterol by CYP11A1 to a single product identified as 7-dehydropregnenolone. Although the physiological importance of these hydroxylated metabolites of D3 and their in vivo formation and mode of action remain to be determined, the rate with which they are formed by CYP11A1 in vitro suggests an important role.

Adrenodoxin↗
PubMed2003

Metabolism and requirements for calcium and phosphorus in the fast-growing chicken as affected by age.

Three series of experiments were conducted with fast-growing chickens in order: to evaluate the effects of dietary Ca and P on cholecalciferol metabolism and expression; to determine dietary Ca requirements; to determine dietary P requirements. The results of the first series confirmed previous results on the effects of dietary Ca and P on some variables of vitamin D metabolism and expression, Ca homeostasis and P metabolism in the young chicken (1- to 21-d-old), and extended them to older birds (22- to 43-d-old). The bone formation rate and the duodenal calbindin content were maintained at high levels until the age of 43 d. Dietary Ca or P restriction increased duodenal calbindin and decreased bone ash in both 22- and 43-d-old chickens, but the effect on bone ash was less pronounced in the 43-d-old birds than in the younger ones. These results suggest that: (a) the capabilities for adaptation to dietary Ca and P restriction remain high during the whole growing period; (b) the growing broilers express a high adaptive capability even when the diet contains the recommended Ca and P contents. The results of the second and third series of experiments suggest that: (c) unlike the Ca requirements of the 1- to 22-d-old chick, P requirements for growth and bone ash are similar, and are as high in the older chicks as in the younger ones (7.4-8.3 g P/kg or 4.8-5.7 g non-phytate P/kg diet); (d) although growth and bone ash in the 29- to 43-d-old chickens appear to be less sensitive to dietary Ca content, within a range close to the calculated P requirement, 10 g Ca/kg diet appears to be required for best tibia mineralization, and to a lesser extent for better growth at this age.

Aging↗
PubMed2003

Effects of u.v. irradiation of very young chickens on growth and bone development.

Six experiments were conducted to study the effects of exposure of young chickens to u.v. radiation. Chickens were fed a cholecalciferol (D3)-deficient diet and exposed to u.v. radiation from fluorescent lights giving total radiance (285-365 nm) at 0.15 m of 99.9 mJ/s per m(2). In Expt 1, chickens had increased body weight, bone ash and plasma Ca and decreased incidence of rickets and tibial dyschondroplasia (TD) when exposed to fluorescent light radiation 24 h per d, 24 h every 2 d, or 24 h every 3 d starting with exposure on day 1 after hatching. However, when not exposed on day 1, but on days 4, 7, 10, 13 and 16, the bone ash was reduced, and the incidence of TD and rickets was increased, compared with chickens exposed on day 1 after hatching. When chickens were exposed at 1 d of age to radiation from two lamps, each of which gave a radiance (285-365 nm) at 0.26 m of 856 mJ/s per m(2), both the length of time of radiation and location of the lamps (above or below the chicken) influenced the response as measured by body weight, bone ash, plasma Ca and incidence of rickets. When chickens that received a TD-inducing diet were exposed to 30 min u.v. radiation from below at 1 d of age they developed significantly less TD than did those not exposed when fed either 27.5 or 55.0 microg D3/kg diet.

Animals↗
PubMed2003

Performance and bone development in broiler chickens given 25-hydroxycholecalciferol.

1. A series of 5 trials was conducted with Cobb chickens in order to determine the effect of 25-hydroxycholecalciferol (25OHD3) on their performance and bone development under adequate Calcium (Ca) and Phosphorus (P) supplementation, and under moderate dietary restriction of Ca and P. Formulated beadlets of 25OHD3, trade name HY-D (IsoGen, Naperville, IL, USA) were used as the 25OHD3 source. 2. Five to 10 microg of cholecalciferol (vitamin D3) or 25OHD3/kg diet were sufficient to ensure normal body weight (BW) and bone ash in chickens under continuous lighting. The two materials had similar effects on BW and bone ash. 3. In one out of the three experiments, 25OHD3 increased BW and BW gain, while in the others it had a similar effect to that of vitamin D3, or even a slight negative effect in a trial conducted on the floor, in which the diets were supplemented with the D sources at 75 microg/kg. The effects of both D sources on bone ash and on the severity or frequency of tibial dischondroplasia were similar. 4. 25OHD3 restrained the effect of moderate dietary P restriction, but not of Ca restriction, on BW gain and bone ash in 22-d-old chickens. This effect could not be explained by an higher P bioavailability in the 25OHD3-fed chickens.

Animal Feed↗
PubMed1998

Vitamin D3 requirement of young chicks receiving diets varying in calcium and available phosphorus.

1. Three battery experiments were conducted with broiler chicks during the 2nd and 3rd week of life. Graded amounts of cholecalciferol (D3) were added to maize-soyabean meal diets that were designed to be (a) severely deficient in available phosphorus (P), (b) marginally deficient in calcium (Ca) or (c) adequate in both available P and Ca. 2. With diets containing 1.0 g available P and 6.3 g Ca/kg (assay 1), graded doses of D3 between 0 and 37.5 mu/kg produced linear (P < 0.05) positive responses in both weight gain and tibia ash. With a D3 concentration of 1250 micrograms/kg, 250 times the requirement recommended by the NRC, bone ash was increased (P < 0.05) over that of birds fed 37.5 micrograms/kg, and neither weight gain nor food intake were reduced. 3. With a P-adequate diet (4.5 g available P/kg) containing 8.5 g Ca/kg (assay 2), weight gain and bone ash increased linearly (P < 0.05) upon supplementing the basal diet with 0, 2.5 and 5.0 micrograms D3/kg. Higher doses of D3 did not elicit further responses, and chicks fed on a diet containing 1250 micrograms D3/kg gained as fast and had bone ash values that did not differ from those of chicks receiving 5, 10, 20 or 40 micrograms D3/kg. 4. When the maize-soyabean meal basal diet was fortified with Ca and P to achieve adequate amounts of Ca (10.1 g/kg) and P (4.5 g available P/kg) in assay 3, dietary additions produced results similar to those obtained in assay 2 where P was adequate and Ca was slightly deficient. Again, chicks receiving a surfeit of D3 (1250 micrograms/kg) exhibited weight gains and bone ash values that were as great as those of chicks receiving 5, 10, 15 or 30 micrograms D3/kg. 5. It is apparent that young chicks have a high tolerance for excess D3, and chicks fed on diets that are severely deficient in available P continue to respond to D3 in excess of 37.5 micrograms/kg.

Analysis of Variance↗
PubMed1979

Nutrition imbalance and angiotoxins as dietary risk factors in coronary heart disease.

Imbalancing nutritionally adequate diets with an excessive amount of fat calories and cholesterol has obscured the fact that intimal thickening occurs spontaneously in time on low-fat cholesterol-free diets during the aging process, and that intimal thickening can be accelerated by dietary angiotoxic "risk factors." Electron microscopy of arterial tissue from animal models identified degenerated smooth muscle cells in the fetus from sows kept on low-fat cholesterol-free diets. After birth, the degenerated smooth muscle cells increased in number with age. The presence of angiotoxic "risk factors" such as oxidized cholesterol and vitamin D3 (cholecalciferol) in the diet of such animal models increased the frequency of smooth muscle cell death in their arteries. Two types of pathology could be developed in the thoracic aorta by continuous or short term feeding of 12.5 times more vitamin D than normally present in commercial rations: 1) a diffuse fibroelastic intimal thickening in the thoracic aorta (arteriosclerosis) with no evidence of lipid deposition by continuous feeding of vitamin D or 2) an initimal thickening in the thoracic aorta and intimal thickening with foam cells and extracellular lipid deposits (atherosclerosis) in the coronary arteries after a short period of supplemental vitamin D followed by 3 to 4 months of supplement-free diets. These two types of arterial damage were identical to that in the plugs of thoracic aorta obtained as a by-product of elective coronary bypass surgery. Although all of the possible sources of oxidized cholesterol in the diet have as yet not been identified, laboratory studies have identified oxidized cholesterol as an angiotoxic factor. Since population groups that consume less vitamin D-supplemented foods, less deep fat fried cholesterol-containing foods, and less hydrogenated fats have a lower incidence of coronary heart disease than Americans, it seems judicious for food processors to reduce these previously unconsidered risk factors to a minimum. This could be done by eliminating vitamin D2 and D3 from all vitamin supplements, from all food and cereal products and from the diet of livestock 1 month before they were killed so that the intake of vitamin D is no larger than the 400 IU/quart in milk which is necessary to prevent rickets in children. Deep fat fryers, which are kept at almost 200 C for 24 hr/day, could perhaps be replaced with microwave ovens in fast food chain outlets. Processors could hydrogenate vegetable oils to a minimum trans fatty acid content and rearrange this fat with polyunsaturated fats to produce high polyunsaturated fats trans-free margarines and shortenings.

Aging↗