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Effect of different doses of vitamin d on serum cholesterol and triglyceride levels in healthy men
Atherosclerosis
313
Elsevier Publishing Company, Amsterdam - Printed in The Netherlands
EFFECT
OF DIFFERENT
CHOLESTEROL
DOSES
OF VITAMIN
AND TRIGLYCERIDE
L. A. CARLSON,
H. DERBLOM
Department of Geriatrics,
AND
LEVELS
D ON SERUM IN HEALTHY
MEN
A. LANNER
University of Uppsala, King Gustaf Vth Research Institute,
Stockholm, and Pharmacia AB,
Uppsala (Sweden)
(Received June lst, 1970)
SUMMARY
Following studied without
reports that vitamin
D increases
the effect in man of treatment vitamin
D, (b) the same preparation
the same preparation 32 and 46 healthy The average
with 1000 I.U. vitamin
men respectively serum cholesterol
the levels of cholesterol
in serum, we
for 6 weeks with (a) a multivitamin/preparation with 500 I.U. vitamin
D per day, (c)
D per day. The groups consisted
of 43,
with an average age of 35 years. level before treatment was 225 mg/lOO ml. After
treatment the serum cholesterol had decreased significantly by 18.3 f 3.9,22.1 & 4.5 and 16.1 f 4.5 mg/lOO ml respectively in the three treatment groups. The differences between groups a, b and c were not significant. The concentration of triglycerides, which on the average groups. levels.
was 1.44 mmol/l
It was concluded
Key words:
that
vitamin
before treatment,
unchanged
in all
D had not had any effect on theserum
lipid
Serzlm cholesterol - Serum triglycerides
remained
- Vitamin D
INTRODUCTION
Clinical manifestations of atherosclerosis develop at a rate which is, amongst other things, related to the concentration of cholesterol in the blood serum. It is thus undesirable for persons to be exposed to factors that increase the serum cholesterol level. It has been reported that vitamin D increases serum cholesterol levels not only in experimental animals1 but also in man 21~. Furthermore after feeding rats with vitamin D, DALDERuP4 found that the liver and vascular lesions contained more cholesterol. Early report@ on calcification and lipid infiltration of the arterial wall after administration of vitamin D to rabbits have recently7 been confirmed. FORFAR AND TOMPSETT* have discussed a possible correlation between hypercholesterolaemia, Atherosclerosis,
1970, 12: 313-317
314
SHORT COMMUNICATIONS
idiopathic studied
hypercalcaemia
of infancy
the effect of vitamin
multivitamin
tablets)
men. MATERIAL
and vitamin
D (in amounts
D. Against
corresponding
on the serum cholesterol :
this background
we
to those present in common
and triglyceride
levelsin
adult healthy
AND METHODS
One hundred
and twenty-one
male subjects
were ranked
according
to age and
divided into three groups (A, B and C), in such a way that the mean age in all three groups was approximately the same. All subjects felt healthy and none had suffered from any recent illness and all were engaged in their usual activities. Each subject took daily for 6 weeks from the beginning of May, a multivitamin tablet containing Vitamin
A 5000 I.U., thiamine
2 mg, calcium
pantothenate
contained no vitamin vitamin Ds.
2 mg, riboflavin
8 mg, ascorbic
Ds, group B tablets
2 mg, niacinamide
acid 75 mg. The tablets contained
20 mg, pyridoxine given to group A
500 I.U. and group C 1000 I.U.
In the event of a subject forgetting to take a tablet instructions were given in advance to take two tablets on the following day. There were no dietary or other restrictions. Venous blood samples were taken between 8 and 10 a.m. after fasting overnight. The blood was allowed to clot at room temperature for l-2 h. Serum was frozen and stored in a deep freezer no longer than 2 months. Both the initial and the treatment serum samples were analysed cholesterols and triglycerideslo.
TABLE INITIAL
at the same time
in a Technicon
autoanalyser
for
1 VALUES
FOR
AGE,
WEIGHT/HEIGHT
INDEX
AND
SERUM
LIPIDS
IN THREE
GROUPS
A = vitamins without vitamin D. B = vitamins with 500 I.U. vitamin D/day. C = vitamins 1000 I.U. vitamin D/day. n = number of subjects. Grou$
with
All groups B (n =
range
x
33.9 (22-57)
35.2 (23-61)
34.9 (21-64)
34.6 (21-64)
height(cm) -100
x range
0.931 (0.71-1.29)
0.933 (0.77-1.16)
0.906 (0.74-1.15)
0.922 (0.71-1.29)
Cholesterol (mg/lOO ml)
x range x range
219.7 (166-340)
233.9 (146-360)
222.7 (100-306)
1.48 (0.76352)
1.57 (0.66-4.26)
1.13 (0.58-2.54)
224.6 (100-360) 1.44 (0.58-4.26)
?T range
0.131 (-0.119-0.547)
0.141 (-0.180-0.629)
0.088 (-0.237-0.405)
0.177 (-0.119-0.629)
Age (year)
32)
C (12 = 46)
A (n = 43)
Weight(kg)/
Triglycerides (mmol/l) Triglycerides (log mmol/l)
A therosclevosis, 1970, 12: 313-317
SHORT
315
COMMUNICATIONS
Atherosclevosis,
1970,
12: 313317
316
SHORT COMMUNICATIONS
RESULTS The initial
mean
values
and ranges
of age, weight/height
index
(cm) -100) and serum levels of cholesterol (mg/lOO ml), triglycerides log triglycerides (log mmol/l) of the subjects in the different groups Table 1. There were no significant these initial values. The results creased
differences
between
the three groups with regard to
of the trial are given in Table 2. The serum
significantly
(P <
0.001) in all three
((kg)/height (mmol/l) and are shown in
groups.
cholesterol
The decreases
levels deamong
the
different groups did not however significantly differ. When the groups were subdivided into subjects with cholesterol values above or below 230 mg/lOO ml, the same picture was evident with decreased cholesterol levels in all groups, but again no difference was apparent between the groups. The triglyceride level, on the other hand, was not significantly
changed
during
the period of study in any of the three groups.
more, there were no significant
differences
between
Further-
the groups.
DISCUSSION Under the conditions or triglyceride
of the study,
levels in serum.
vitamin
The lowering
D had no effect on either cholesterol
of serum cholesterol
was similar
in the
group given vitamin tablets without vitamin D to that in the two groups who in addition obtained 500 and 1000 I.U. of vitamin D in the tablets. The reason for the lowered cholesterol in all three groups is unknown. It could be due to one of the constitutents however, values.
of the tablets never altered. For example,
or it could be due to other factors. The triglyceride levels, Seasonal variation might have influenced the cholesterol
CARLSON AND LINDSTEDT II found that
the average cholesterol
values among 1266 healthy men in May, June and July were 273,263 and 248 mg/lOO ml respectively. This decrease is of the same order as that observed in this study. At the same time the values for plasma triglycerides behaved somewhat differently as the mean values observed in May, June and July were 1.49, 1.50 and 1.25 mmol/l respectively. Thus, the triglyceride levels did not change from May to June. The reason for the different results in these studies on the effect of vitamin D on serum cholesterol levels and those in previous studie+s is not clear, but may be due to factors such as dosage, experimental design, season, etc. We can, however, say that under the conditions of this study vitamin D had no effect on serum cholesterol levels.
REFERENCES 1 DONATH, W.
F. AND C. D. DE LANGEN, Vitamin D sclerosis of the arteries and the danger of feeding extra vitamin D to older people, with a view on the development of different forms of arteriosclerosis, Koninkl. Ned. Akad. Wetenschap., Proc., Sev. C, 1957, 60: 15-21. 2 FEENSTRA, L. AND J. H. WILKENS, Cholesterol en vitamine D, Ned. T. Geneesk., 1965, 109:
615-619.
3 DALDERUP, L. M., Cholesterol en vitamine D, Ned. T. Geneesk., 1965, 109: 770-771. 4 DALDERUP, L. M., Vitamin D, cholesterol, and calcium, Lancet, 1968, i: 645-646.
Atherosclerosis,
1970, 12: 313-317
SHORT
317
COMMUNICATIONS
PFLEIDERER, E., Tierexperimentelle Untersuchungen iiber Arteriosklerose unter besonderer Beriicksichtinuna der Kranzarteriensklerose. Vi’ivchows Arch. Path. Anat., 1932, 284: 154-174. LAAS, E., D1’: Aiflnge der Vigantolschadigung beim Kaninchen, Virchows Arch. Path. Anat., 1930, 278: 346-354. EISENSTEIN, R. AND L. ZERUOLIS, Vitamin D-induced aortic calcification, Arch. Pathol., 1964, 77: 27-35. FORFAR, J. 0. AND L. TOMPSETT, Idiopathic hypercalcemia of infancy, Advan. Clin. Chem., 1959, 2: 167-200. BLOCK, W. D., K. J. JARRETT AND B. LEOINE, Use of a single color reagent to improve the in automated determination of serum total cholesterol. In: L. T. SKEGGS (Ed.), Automation Analytical Chemistry, Vol. 1, Medical Incorporated, New York, 1965, pp. 345-347. KESSLER, G. AND H. LEDERER, Fluorometric measurement of triglycerides. In: L. T. SKEGGS (Ed.), Automation in Analytical Chemistry, Vol. 1, Medical Incorporated, New York, 1965, pp. 341-344. CARLSON, L. A. AND S. LINDSTEDT, The Stockholm prospective study, Part 1 (The initial values for plasma lipids), Acta Med. Stand., Suppl. 493, 1968.
Atherosclerosis,
1970, 12: 313-317
313
Elsevier Publishing Company, Amsterdam - Printed in The Netherlands
EFFECT
OF DIFFERENT
CHOLESTEROL
DOSES
OF VITAMIN
AND TRIGLYCERIDE
L. A. CARLSON,
H. DERBLOM
Department of Geriatrics,
AND
LEVELS
D ON SERUM IN HEALTHY
MEN
A. LANNER
University of Uppsala, King Gustaf Vth Research Institute,
Stockholm, and Pharmacia AB,
Uppsala (Sweden)
(Received June lst, 1970)
SUMMARY
Following studied without
reports that vitamin
D increases
the effect in man of treatment vitamin
D, (b) the same preparation
the same preparation 32 and 46 healthy The average
with 1000 I.U. vitamin
men respectively serum cholesterol
the levels of cholesterol
in serum, we
for 6 weeks with (a) a multivitamin/preparation with 500 I.U. vitamin
D per day, (c)
D per day. The groups consisted
of 43,
with an average age of 35 years. level before treatment was 225 mg/lOO ml. After
treatment the serum cholesterol had decreased significantly by 18.3 f 3.9,22.1 & 4.5 and 16.1 f 4.5 mg/lOO ml respectively in the three treatment groups. The differences between groups a, b and c were not significant. The concentration of triglycerides, which on the average groups. levels.
was 1.44 mmol/l
It was concluded
Key words:
that
vitamin
before treatment,
unchanged
in all
D had not had any effect on theserum
lipid
Serzlm cholesterol - Serum triglycerides
remained
- Vitamin D
INTRODUCTION
Clinical manifestations of atherosclerosis develop at a rate which is, amongst other things, related to the concentration of cholesterol in the blood serum. It is thus undesirable for persons to be exposed to factors that increase the serum cholesterol level. It has been reported that vitamin D increases serum cholesterol levels not only in experimental animals1 but also in man 21~. Furthermore after feeding rats with vitamin D, DALDERuP4 found that the liver and vascular lesions contained more cholesterol. Early report@ on calcification and lipid infiltration of the arterial wall after administration of vitamin D to rabbits have recently7 been confirmed. FORFAR AND TOMPSETT* have discussed a possible correlation between hypercholesterolaemia, Atherosclerosis,
1970, 12: 313-317
314
SHORT COMMUNICATIONS
idiopathic studied
hypercalcaemia
of infancy
the effect of vitamin
multivitamin
tablets)
men. MATERIAL
and vitamin
D (in amounts
D. Against
corresponding
on the serum cholesterol :
this background
we
to those present in common
and triglyceride
levelsin
adult healthy
AND METHODS
One hundred
and twenty-one
male subjects
were ranked
according
to age and
divided into three groups (A, B and C), in such a way that the mean age in all three groups was approximately the same. All subjects felt healthy and none had suffered from any recent illness and all were engaged in their usual activities. Each subject took daily for 6 weeks from the beginning of May, a multivitamin tablet containing Vitamin
A 5000 I.U., thiamine
2 mg, calcium
pantothenate
contained no vitamin vitamin Ds.
2 mg, riboflavin
8 mg, ascorbic
Ds, group B tablets
2 mg, niacinamide
acid 75 mg. The tablets contained
20 mg, pyridoxine given to group A
500 I.U. and group C 1000 I.U.
In the event of a subject forgetting to take a tablet instructions were given in advance to take two tablets on the following day. There were no dietary or other restrictions. Venous blood samples were taken between 8 and 10 a.m. after fasting overnight. The blood was allowed to clot at room temperature for l-2 h. Serum was frozen and stored in a deep freezer no longer than 2 months. Both the initial and the treatment serum samples were analysed cholesterols and triglycerideslo.
TABLE INITIAL
at the same time
in a Technicon
autoanalyser
for
1 VALUES
FOR
AGE,
WEIGHT/HEIGHT
INDEX
AND
SERUM
LIPIDS
IN THREE
GROUPS
A = vitamins without vitamin D. B = vitamins with 500 I.U. vitamin D/day. C = vitamins 1000 I.U. vitamin D/day. n = number of subjects. Grou$
with
All groups B (n =
range
x
33.9 (22-57)
35.2 (23-61)
34.9 (21-64)
34.6 (21-64)
height(cm) -100
x range
0.931 (0.71-1.29)
0.933 (0.77-1.16)
0.906 (0.74-1.15)
0.922 (0.71-1.29)
Cholesterol (mg/lOO ml)
x range x range
219.7 (166-340)
233.9 (146-360)
222.7 (100-306)
1.48 (0.76352)
1.57 (0.66-4.26)
1.13 (0.58-2.54)
224.6 (100-360) 1.44 (0.58-4.26)
?T range
0.131 (-0.119-0.547)
0.141 (-0.180-0.629)
0.088 (-0.237-0.405)
0.177 (-0.119-0.629)
Age (year)
32)
C (12 = 46)
A (n = 43)
Weight(kg)/
Triglycerides (mmol/l) Triglycerides (log mmol/l)
A therosclevosis, 1970, 12: 313-317
SHORT
315
COMMUNICATIONS
Atherosclevosis,
1970,
12: 313317
316
SHORT COMMUNICATIONS
RESULTS The initial
mean
values
and ranges
of age, weight/height
index
(cm) -100) and serum levels of cholesterol (mg/lOO ml), triglycerides log triglycerides (log mmol/l) of the subjects in the different groups Table 1. There were no significant these initial values. The results creased
differences
between
the three groups with regard to
of the trial are given in Table 2. The serum
significantly
(P <
0.001) in all three
((kg)/height (mmol/l) and are shown in
groups.
cholesterol
The decreases
levels deamong
the
different groups did not however significantly differ. When the groups were subdivided into subjects with cholesterol values above or below 230 mg/lOO ml, the same picture was evident with decreased cholesterol levels in all groups, but again no difference was apparent between the groups. The triglyceride level, on the other hand, was not significantly
changed
during
the period of study in any of the three groups.
more, there were no significant
differences
between
Further-
the groups.
DISCUSSION Under the conditions or triglyceride
of the study,
levels in serum.
vitamin
The lowering
D had no effect on either cholesterol
of serum cholesterol
was similar
in the
group given vitamin tablets without vitamin D to that in the two groups who in addition obtained 500 and 1000 I.U. of vitamin D in the tablets. The reason for the lowered cholesterol in all three groups is unknown. It could be due to one of the constitutents however, values.
of the tablets never altered. For example,
or it could be due to other factors. The triglyceride levels, Seasonal variation might have influenced the cholesterol
CARLSON AND LINDSTEDT II found that
the average cholesterol
values among 1266 healthy men in May, June and July were 273,263 and 248 mg/lOO ml respectively. This decrease is of the same order as that observed in this study. At the same time the values for plasma triglycerides behaved somewhat differently as the mean values observed in May, June and July were 1.49, 1.50 and 1.25 mmol/l respectively. Thus, the triglyceride levels did not change from May to June. The reason for the different results in these studies on the effect of vitamin D on serum cholesterol levels and those in previous studie+s is not clear, but may be due to factors such as dosage, experimental design, season, etc. We can, however, say that under the conditions of this study vitamin D had no effect on serum cholesterol levels.
REFERENCES 1 DONATH, W.
F. AND C. D. DE LANGEN, Vitamin D sclerosis of the arteries and the danger of feeding extra vitamin D to older people, with a view on the development of different forms of arteriosclerosis, Koninkl. Ned. Akad. Wetenschap., Proc., Sev. C, 1957, 60: 15-21. 2 FEENSTRA, L. AND J. H. WILKENS, Cholesterol en vitamine D, Ned. T. Geneesk., 1965, 109:
615-619.
3 DALDERUP, L. M., Cholesterol en vitamine D, Ned. T. Geneesk., 1965, 109: 770-771. 4 DALDERUP, L. M., Vitamin D, cholesterol, and calcium, Lancet, 1968, i: 645-646.
Atherosclerosis,
1970, 12: 313-317
SHORT
317
COMMUNICATIONS
PFLEIDERER, E., Tierexperimentelle Untersuchungen iiber Arteriosklerose unter besonderer Beriicksichtinuna der Kranzarteriensklerose. Vi’ivchows Arch. Path. Anat., 1932, 284: 154-174. LAAS, E., D1’: Aiflnge der Vigantolschadigung beim Kaninchen, Virchows Arch. Path. Anat., 1930, 278: 346-354. EISENSTEIN, R. AND L. ZERUOLIS, Vitamin D-induced aortic calcification, Arch. Pathol., 1964, 77: 27-35. FORFAR, J. 0. AND L. TOMPSETT, Idiopathic hypercalcemia of infancy, Advan. Clin. Chem., 1959, 2: 167-200. BLOCK, W. D., K. J. JARRETT AND B. LEOINE, Use of a single color reagent to improve the in automated determination of serum total cholesterol. In: L. T. SKEGGS (Ed.), Automation Analytical Chemistry, Vol. 1, Medical Incorporated, New York, 1965, pp. 345-347. KESSLER, G. AND H. LEDERER, Fluorometric measurement of triglycerides. In: L. T. SKEGGS (Ed.), Automation in Analytical Chemistry, Vol. 1, Medical Incorporated, New York, 1965, pp. 341-344. CARLSON, L. A. AND S. LINDSTEDT, The Stockholm prospective study, Part 1 (The initial values for plasma lipids), Acta Med. Stand., Suppl. 493, 1968.
Atherosclerosis,
1970, 12: 313-317