Santa Fe Center for Allergy & Environmental Medicine, Director Santa Fe, USA
Abstract
Background
Asthma is an increasing problem in this country and others. Although medications for the treatment of asthma abound and are improving, there are inherent risks and side effects with all of them. Intravenous magnesium has been employed in the treatment of acute asthma, but its use has not become universal, nor has it been studied for the treatment of chronic asthma. It is known to be a safe drug with minimal side effects. In this study, the author investigates the use of magnesium and other nutrients in the treatment of both acute and chronic asthma.
Methods
In this non-blinded outcome study, following informed consent, forty-three (43) randomly selected volunteer patients with both acute and chronic asthma were treated with IV infusions described herein. All patients were observed with spirometry 10 minutes post-infusion; two sub-groups of patients were also observed after multiple infusions over a short period of time (less than one month) and a longer period of time (average 5.8 months). Pulmonary function was analyzed by spirometric testing with pre- and post-infusion spirometric measurements with the pre/post group. For longer term (Trend) patients, baseline spirometry measurements were compared to spirometry measurements after patients had received multiple infusions over a period of time. Eight (8) patients were measured for both pre/post and Trend data.
Results
The 38 pre-infusion/post-infusion patients with acute and chronic asthma demonstrated an overall average improvement (percentage improvement in percent predicted) of 45%. The 13 patients measured for improvement over time (Trend data, average duration 5.82 months), demonstrated an overall average improvement (percentage improvement in percent predicted) of 57%. Of the 13 patients in the multiple infusion group, 9 patients who received longer-term therapy (average duration of 12.58 months) for chronic asthma demonstrated an overall average improvement of 95% (percentage improvement in percent predicted).
Conclusion
The use of intravenous treatment with multiple nutrients, including magnesium, for acute and chronic asthma may be of considerable benefit. Pulmonary function improved progressively the longer patients received treatment.
Background
Asthma has been a major focus for physicians in recent years because both the incidence and the mortality appear to be increasing, especially within certain ethnic or geopolitical groups
In addition, asthma has become increasingly more difficult to treat. Several studies indicate the mortality of asthma is higher and that the incidence of status asthmaticus patients seen in emergency rooms has increased
In view of these rather grim realizations and statistics, the author has undertaken research of a modality in an attempt to mitigate the effects of asthma. A most promising treatment appears to be intravenous therapy with magnesium and other nutrients, both for the acute and chronic illness.
The use of IV parenteral nutrient therapy for asthma was begun in the author's office in the late 1980's, soon after the first papers appeared in the literature involving the use of IV magnesium for the treatment of acute asthma
The author's IV protocols were expanded based on studies of the theoretical and known effects of various other nutrients on both acute and chronic asthma, as a result of previous work with general parenteral nutrients. Dr. Jonathan Wright's work with molybdenum
Methods
This study began with a total of 49 patients who came to the author's clinic for treatment from 1989 through 1998. These patients all had moderate to severe (steroid-dependent) asthma, and all required one or more medications for asthma. Patients were asked to volunteer for the study, and all signed appropriate informed consent documents. Not all patients treated in the clinic volunteered for the study, and no patient who volunteered was excluded unless therapy appeared to fail.
During the study, 6 patients showed no initial response to the first treatment. These 6 patients were considered non-responders and were not included in the data pool in this study, since there was no measurable improvement with a trial infusion. Forty-three (43) patients of mixed Caucasian descent were eventually enrolled, consisting of 16 males and 27 females, with a combined average age of 53 years.
Patients evaluated for pre- and post infusion results were given the IV "Push" protocol indicated in Table
Intravenous Protocols Used for Acute and Chronic Asthma
Nutrient
mOsm/ml
"Push" Protocol (ml)
Infusion Protocol (ml)
Ascorbic acid 500 mg./ml
5.8
3
12
B-12 (hydroxycobalamine) 1000 mcg./ml
.30
1
1
B-6 (pyridoxine) 100 mg./ml
1.11
2
5
B-complex 100 mg./ml
2.14
2
2
Calcium gluconate 10% (100 mg./ml)
.72
2
2
Magnesium sulfate 500 mg./ml
4.06
4–5
5–6
Mineral mix **
.57
1
Molybdenum 500 mcg./ml
.10
1
Pantothenic acid ("B-5") 250 mg./ml
.85
2
2
Sterile Water
0
13–14
250
** Mineral mix formulation: Copper 1 mg./ml, chromium 50 mcg./ml, manganese 100 mcg./ml, molybdenum 250 mg./ml, selenium 200 mcg./ml, vanadium 100 mcg./ml, zinc 5 mg./ml.
Thirteen (13) patients were given the Infusion (Table
All patients were evaluated pre- and post-IV treatment with spirometry (pulmonary function testing, or PFT), using the SX-Platinum® computerized pulmonary function testing program. Spirometry was done immediately (within 10 minutes) after the protocols were administered. The computerized results were based on predicted Knudson normal for age, sex, weight and height.
The Trend group was further divided into "Short Term" and "Long Term" groups. The Short Term group consisted of those patients who had "trend" data measured for one month or less, while those in the Long Term group were treated for up to 19 months. There were 4 patients in the Short Term group, 3 females and 1 male, average age 62, with an average duration of therapy of 0.43 mos. and 3.25 infusions per patient. There were 9 patients in the Long Term group, 6 females and 3 males, average age 53, with an average duration of therapy 12.58 mos. and 9.25 infusions per patient.
The average length of treatment periods for combined Trend patients was 5.82 months, with the shortest being 0.2 months. IV's were given anywhere from twice weekly to once every few months, with an average of 6.77 IV's per patient, or 1.16 IV's per patient per month.
Parameters monitored in all patients were Total Forced Vital Capacity (FVC), Forced Expiratory Flow in 1 second (FVC 1.0), Peak Expiratory Flow (PEF), Forced Expiratory Flow through 25% to 75% of exhalation (FEF 25–75%) and Forced Expiratory Flow through 75% to 85% of exhalation (FEF 75–85%).
Preservative-free nutrients were used without exception, and there were no serious systemic and no local reactions at any time during therapy. Early in the study some patients experienced lightheadedness, nausea or near fainting with rapid IV infusions. This was secondary to magnesium-induced hypotension, and this problem was recognized early in the study and avoided.
Results
Results were measured as percentage improvement of the percentage predicted on the Knudsen scale. For example, if the result of a parameter of the pre-infusion pulmonary function test was calculated as 50% of predicted normal, and IV treatment resulted in a value of 75% of predicted normal for that same parameter, the percentage improvement for that particular parameter would be entered as 50%.
The 38 pre-infusion/post-infusion patients demonstrated an average improvement of 28% in FVC, 44% in FEV 1, 44% in PEF, 54% in FEF 25–75 and 38% in FEF 75–85, with an overall average improvement of 45% (Tables
Pre-/Post IV Treatment Data – 39 Patients Percent Predicted, Pre- and Post- infusion with % improvement
FVC (L)
FEV 1 (L)
PEF (L/S)
FEF 25–75 (L/S)
FEF 75–85 (L/S)
Sex
Age
% Predicted
% Predicted
% Predicted
% Predicted
% Predicted
Patient
Pre
Post
%
Pre
Post
%
Pre
Post
%
Pre
Post
%
Pre
Post
%
A, L.
M
55
36
72
100%
36
79
119%
64
92
44%
35
129
269%
32
112
250%
A, S.
F
48
28
50
79%
30
48
60%
40
78
95%
30
40
33%
40
38
-5%
B, M.
F
57
69
100
45%
48
81
69%
45
115
156%
24
39
63%
30
32
7%
B, R.
M
46
73
93
27%
69
87
26%
95
106
12%
57
70
23%
66
67
2%
B, V.
F
39
34
67
97%
34
72
112%
51
59
16%
38
96
153%
26
98
277%
B, V.
F
70
38
54
42%
32
47
47%
32
53
66%
18
30
67%
25
34
36%
C, D.
M
59
27
30
11%
14
17
21%
10
12
20%
10
10
0%
32
28
-13%
C, A.
F
33
90
91
1%
80
98
23%
115
142
23%
60
108
80%
65
116
78%
C, K.
F
35
45
62
38%
34
52
53%
32
56
75%
22
36
64%
32
41
28%
D, C.
F
33
65
65
0%
49
56
14%
62
65
5%
31
41
32%
42
51
21%
D, B.
M
49
65
80
23%
72
83
15%
68
88
29%
75
80
7%
146
147
1%
D, K.
F
48
61
74
21%
56
70
25%
89
95
7%
39
60
54%
29
33
14%
F, L.
M
58
26
29
12%
12
13
8%
7
8
14%
7.4
8.1
9%
22
26
18%
G, W.
M
74
48
67
40%
25
57
128%
16
88
450%
11
37
236%
38
63
66%
G, B.
M
45
83
113
36%
83
101
22%
94
149
59%
81
70
-14%
89
60
-33%
G, G.
F
42
83
93
12%
46
82
78%
24
59
146%
31
66
113%
55
79
44%
G, L.
F
63
50
78
56%
36
60
67%
52
71
37%
17
29
71%
21
29
38%
J, E.
F
63
47
85
81%
38
84
121%
43
64
49%
19
79
316%
20
55
175%
K, H.
F
49
58
72
24%
59
72
22%
82
99
21%
53
62
17%
76
86
13%
M, A.
F
46
85
97
14%
79
89
13%
61
86
41%
71
71
0%
73
68
-7%
M, W.
M
85
74
77
4%
69
90
30%
46
82
78%
50
119
138%
148
458
209%
M, C.
F
36
93
85
-9%
52
53
2%
30
46
53%
26
25
-4%
26
25.5
-2%
M, J.
M
64
74
75
1%
49
57
16%
47
60
28%
25
37
48%
57
83
46%
O, M
F
49
90
99
10%
98
114
16%
88
167
90%
114
168
47%
145
214
48%
P, O.
F
47
54
72
33%
52
76
46%
85
84
-1%
46
82
78%
40
74
85%
R, B.
F
69
21
23
10%
16
19
19%
13
17
31%
10
11
10%
21
22
5%
S, M.
F
60
56
94
68%
45
88
96%
60
104
73%
26
66
154%
26
51
96%
S, J.
M
54
98
166
69%
76
96
26%
77
70
-9%
34
39
15%
70
90
29%
S, S.
M
40
73
85
16%
58
69
19%
68
85
25%
36
40
11%
43
38
-12%
S, D.
F
64
40
56
40%
25
33
32%
18
21
17%
15
14
-7%
42
34
-19%
S, W.
M
44
71
80
13%
52
65
25%
42
60
43%
31
40
29%
31
38
23%
T, P.
F
45
41
59
44%
26
46
77%
22
73
232%
17
27
59%
26
32
23%
W, P.
F
65
48
76
58%
17
31
82%
9
21
133%
9
11
22%
20
19
-3%
W, B.
M
38
54
72
33%
42
58
38%
32
46
44%
25
37
48%
37
50
35%
W, R.
M
40
77
77
0%
34
41
21%
27
33
22%
12
16
33%
21
24
14%
W, C.
F
55
28
39
39%
20
28
40%
17
26
53%
12
16
33%
20
23
15%
W, G.
F
70
101
108
7%
78
98
26%
34
82
141%
51
65
27%
49
62
27%
Z, A.
F
43
62
75
21%
64
75
17%
107
87
-19%
68
88
29%
57
49
-14%
Average:
52
60
76
28%
48
65
38%
50
72
44%
35
54
54%
48
70
44%
Average Overall Improvement
45%
Results were measured as percentage improvement of the percentage predicted on the Knudsen scale
Summary, Pre- and Post-IV Treatment Spirometry Results – 39 patients (Acute Asthma Protocol) Acute Asthma Pre- and Post-infusion Values Measured in Percent Predicted
Parameter
Pre-IV
Post-IV
Ave. % Improved
FVC (L)
60
76
28%
FEV 1 (L)
48
65
38%
PEF (L/S)
50
72
44%
FEF 25–75 (L/S)
35
54
54%
FEF 75–85 (L/S)
48
70
44%
Total Average Improvement
45%
Results were measured as percentage improvement in the percentage predicted on the Knudsen scale
The 13 patients measured for improvement over time (sequential data, average duration 5.82 months with an average of 1.66 infusions/patient/mo.) for chronic asthma showed an average improvement of 50% in FVC, 57% in FEV 1, 64% in PEF, 64% in FEF 25–75 and 44% in FEF 75–85, with an overall average improvement of 57% (Tables
Trend Data – 13 Patients
% Predicted
% Predicted
% Predicted
% Predicted
% Predicted
Patient
FVC (L)
FEV 1 (L)
PEF (L/S)
FEF 25–75 (L/S)
FEF 75–85 (L/S)
Sex
Age
Mos.
# IVs per pt.
Pre
Post
%
Pre
Post
%
Pre
Post
%
Pre
Post
%
Pre
Post
%
B, M.
F
57
9.5
11
73
97
33%
56
78
39%
89
109
22%
26
41
58%
29
40
38%
B, C
M
31
2.3
8
34
97
185%
39
69
77%
30
53
77%
17
45
165%
13
52
300%
D, K
F
16
5.3
11
119
143
20%
94
96
2%
95
134
41%
54
37
-31%
Not done
G, W.
M
74
3.5
4
48
67
40%
25
57
128%
16
93
481%
11
34
209%
38
54
42%
G, L.
F
63
3
4
50
82
64%
36
65
81%
51
56
10%
17
35
106%
21
36
71%
H, K.
F
55
5.3
11
61
105
72%
41
97
137%
56
120
114%
18
38
111%
20
43
115%
L, L.
F
53
0.3
2
40
87
118%
42
69
64%
50
47
-6%
38
47
24%
62
49
-21%
O, M.
F
48
19
4
72
90
25%
63
98
56%
60
88
47%
42
114
171%
42
145
245%
P, R.
M
77
1
6
65
88
35%
66
89
35%
73
92
26%
57
80
40%
165
171
4%
R, B.
F
49
0.2
3
59
72
22%
59
71
20%
44
80
82%
61
70
15%
67
49
-27%
S, L.
F
64
10
9
61
86
41%
41
64
56%
73
113
55%
16
24
50%
27
22
-19%
S, W.
M
44
16
13
45
98
118%
35
77
120%
34
98
188%
21
45
114%
31
46
48%
W, G.
F
70
0.2
2
65
74
14%
38
64
68%
16
47
194%
20
42
110%
21
64
205%
Average
54
5.82
6.77
61
91
50%
49
76
57%
53
87
64%
31
50
64%
45
64
44%
Ave. # IVs per patient per month
1.16
Average Overall Improvement
57%
Results were measured as percentage improvement in the percentage predicted on the Knudsen scale
Trends in Patients with Chronic Asthma – 13 patients Trend Values Measured in Percent Predicted
Parameter
Beginning of Therapy
Conclusion of Therapy
Ave. % Improved
FVC (L)
61
91
50%
FEV 1 (L)
49
76
57%
PEF (L/S)
53
87
64%
FEF 25–75 (L/S)
31
50
64%
FEF 75–85 (L/S)
45
64
44%
Total Average Improvement
57%
Trend values were obtained by subtracting the results of the first spirometry testing in the series from the results of the last (most current) in the series. Results were measured as percentage improvement in the percentage predicted on the Knudsen scale.
Of the 13 patient multiple infusion group, 4 patients who received Short Term therapy (infusions for an average duration of a month or less) for chronic asthma demonstrated an average improvement of 40% in FVC, 43% in FEV 1, 45% in PEF, 36% in FEF 25–75 and 6% in FEF 75–85, with an overall average improvement of 34% (Table
Short-term Trend Data (infusions for one month or less) 4 Patients
% Predicted
% Predicted
% Predicted
% Predicted
% Predicted
FVC (L)
FEV 1 (L)
PEF (L/S)
FEF 25–75 (L/S)
FEF 75–85 (L/S)
Patient
Sex
Age
Mos.
# IVs per pt.
Pre
Post
%
Pre
Post
%
Pre
Post
%
Pre
Post
%
Pre
Post
%
L, L.
F
53
0.3
2
40
87
118%
42
69
64%
50
47
-6%
38
47
24%
62
49
-21%
P, R.
M
77
1
6
65
88
35%
66
89
35%
73
92
26%
57
80
40%
165
171
4%
R, B.
F
49
0.2
3
59
72
22%
59
71
20%
44
80
82%
61
70
15%
67
49
-27%
W, G.
F
70
0.2
2
65
74
14%
38
64
68%
16
47
194%
20
42
110%
21
64
205%
Average
62
0.43
3.25
57
80
40%
51
73
43%
46
67
45%
44
60
36%
79
83
6%
Ave. # IVs per patient
3.25
Average Overall Improvement
34%
Short Term
Results were measured as percentage improvement in the percentage predicted on the Knudsen scale
Long-term Trend Data (infusion for over a month) 9 Patients
% Predicted
% Predicted
% Predicted
% Predicted
% Predicted
Patient
FVC (L)
FEV 1 (L)
PEF (L/S)
FEF 25–75 (L/S)
FEF 75–85 (L/S)
Sex
Age
Mos.
# IVs Per pt.
Pre
Post
%
Pre
Post
%
Pre
Post
%
Pre
Post
%
Pre
Post
%
B, M.
F
57
9.5
11
73
97
33%
56
78
39%
89
109
22%
26
41
58%
29
40
38%
B, C
M
31
2.3
8
34
97
185%
39
69
77%
30
53
77%
17
45
165%
13
52
300%
D, K
F
16
5.3
11
119
143
20%
94
96
2%
95
134
41%
54
37
-31%
Not done
G, W.
M
74
3.5
4
48
67
40%
25
57
128%
16
93
481%
11
34
209%
38
54
42%
G, L.
F
63
3
4
50
82
64%
36
65
81%
51
56
10%
17
35
106%
21
36
71%
H, K.
F
55
5.3
11
61
105
72%
41
97
137%
56
120
114%
18
38
111%
20
43
115%
O, M.
F
48
19
4
72
90
25%
63
98
56%
60
88
47%
42
114
171%
42
145
245%
S, L.
F
64
10
9
61
86
41%
41
64
56%
73
113
55%
16
24
50%
27
22
-19%
S, W.
M
44
16
13
45
98
118%
35
77
120%
34
98
188%
21
45
114%
31
46
48%
Average
53
12.58
9.25
60
95
59%
45
84
87%
56
105
88%
24
55
128%
30
64
113%
Ave. # IVs per patient per month
0.74
Average Overall Improvement
95%
Long Term
Results were measured as percentage improvement in the percentage predicted on the Knudsen scale
Discussion
Although there were no age-matched control patients in this outcome study, and certainly uncontrolled variables, considerable improvement was observed after parenteral infusion therapy with multiple nutrients, both for pre/post treatment and treatment over time. There was more pronounced improvement after longer-term treatment. Patients who received treatment for longer than a month fared considerably better than those who stopped therapy within a month or less.
Patients experienced rapid clinical relief during – or at some time after – most infusions, depending on their degree of distress, and as the data demonstrates, pulmonary function improved overall during the sequential infusion study. It would also appear that the effectiveness of this type of therapy might be cumulative, as patients appeared to require treatment less often as time passed. Drug usage was decreased in all patients, and discontinued or reduced to intermittent use in over half of the patients studied.
The primary reason mixed nutrients were employed in this study is that prior to this study the author had observed that the effect of a combination of nutrients was consistently more beneficial than the infusion of IV magnesium sulfate alone. Patients given magnesium (sulfate) alone also seemed to develop a more rapidly increasing tolerance for (or resistance to) magnesium, and pulmonary function did not improve nearly as significantly as were those of patients who were given the complete protocols. Therefore, infusions of magnesium sulfate alone, without other nutrients added, was not employed in this study.
It has been demonstrated previously that intravenous infusions with magnesium sulfate appear to be more effective that nebulized albuterol alone
There are numerous metabolic and biochemical explanations as to why each of the specific nutrients added might indeed provide more benefit for asthmatics than magnesium sulfate alone. For example, Vitamin C is known to have a general antihistaminic effect
Trace minerals also mitigate the inflammatory response
Lastly, zinc is an essential trace mineral for most immune mechanisms in the body to function, including lymphocyte (T-cell) function
This reasoning could partly explain why the patients in this study who received longer-term therapy with infusions fared best. Molybdenum, as Wright's study demonstrated
Over the period of this study, the author observed that 6 of 44 asthmatic patients appeared to fail with this particular type of infusion therapy. These 6 patients, however, were judged as failures prior to any patient having received three IV treatments. Since this study was undertaken, the author has found that it sometimes takes 3 to 5 infusions for patients to observe a substantial clinical benefit. Therefore, actual failure may be in question.
Shortly after this study was first begun, it became clear that patients who received weekly or more frequent therapy with these parenteral nutrients for a period of 1 1/2 to 3 months improved more rapidly and distinctly than patients who received only occasional infusions. It also became evident that this group of patients was able to extend the interval between treatments to 8–14 days and then longer. Several patients were able to extend their intervals out as far as 4–6 months with little apparent loss of efficacy.
This led the author to reach the preliminary conclusion that there may be some type of "loading" period, or dose accumulation, of one or more of these nutrients employed here. Dr. Wright, working with intravenous molybdenum for asthma, discovered this same phenomenon
It was also often observed that patients with acute asthma sometimes did not improve immediately, or even appeared to worsen immediately after an infusion. This is very likely secondary to the acute bronchodilitation resulting from this treatment, with resultant mucous production (release) and coughing. Studies have shown that optimal pulmonary function is likely to occur considerably later than 10 minutes after an infusion of magnesium, even out to perhaps 80–110 minutes
As a more important note, the author observed that the Infusion protocol, when given as the initial treatment, whether for a patient with acute or chronic asthma, could cause considerable worsening of symptoms several hours after the infusion. Early in the study, three patients who were given the Infusion as their first treatment experienced increased respiratory distress later in the day, two of which required emergency treatment. The author postulates that the infusion administration of either the molybdenum or the trace minerals (containing molybdenum) prior to "priming" a patient with at least one IV that does not contain minerals can cause an adverse reaction. Although the mechanism of this reaction is not yet clear, the author speculates this response may be secondary to an acute sulfite detoxification response to molybdenum.
Considering this, the author advises that neither trace minerals nor molybdenum be included in any rapidly infused IV or in any IV to be administered for acute asthma.
The author would conclude that parenteral infusion therapy with the nutrients used in this study might have considerable benefit. Infusions of these particular parental nutrients very often made the difference for patients who otherwise were responding poorly to other modalities of treatment.
As a result of this study, the author is of the opinion that this type of therapy adds a dimension to the treatment of chronic asthma not attainable with conventional therapy using bronchodilators and corticosteroids, especially in the acute situation.
In a time when multiple factors appear to be coalescing to increase both the incidence and morbidity of asthma around the world, it would seem that any therapy that adds a measure of exclusion from these statistics should be considered whenever possible.
Acknowledgements
Susan Ung, RN, Peggy Maltese, Jana Boggs, Allee Jay, RN, Diane Menzies, Patti Robinson and Barbara Shrader for their help in collecting the data for this study.