Consequences of vascular or mitochondrial disorders?
The findings of an association between spontaneous abortion and
maternal risk of ischaemic heart disease (1) and that drinking coffee
during pregnancy is associated with an increased risk of stillbirth but
not with infant death (2) are consistent with the hypothesis that fetal
and infant wellness are dependent upon the adequacy of mitochondrial
oxidative phosphorylation (3). That some studies have shown that folate
supplements reduce the risk of neural tube defects and others have shown
that it does not (4) would also be consistent with this hypothesis if the
beneficial effects of the supplement were to be shown to be due to the
effects of the potent xanthine oxidase inhibitor contaminating commercial
preparations of folate rather than the folate per se (5). The findings are
also consistent with the hypothesis that an inadequacy of mitochondrial
oxidative phosphorylation is the principle cause of acute and chronic
organ dysfunctions and failures and nosocomial infections in adults (6-
12).
Occult cardiovascular, microvascular, or haemostatic dysfunction may
in themselves be the products of an impairment of mitochondrial oxidative
phosphorylation in the intima and/or media (10,11). It which case it is
likely to be an inadequacy of mitochondrial oxidative phosphoprylation
rather than vascular and haematologic diseases, as proposed (1), that
result in "pregnancy complications during reproductive years and in overt
cardiovascular disease in later life". As the occult cardiovascular,
microvascular, or haemostatic dysfunction may also impair oxygen delivery
to cells they may, however, be a secondary cause of an inadequacy of
oxidative phosphoprylation.
In future stusies all causes of an inadequacy of oxidative
phosphorylation need to be considered including the effects of food which
are not unlike the effects of phosphodiesterase inhibitors such as
caffiene (14,15). Both food and caffiene may cause a transient impairment
or transient increase in the severity of an impairment of mitochondrial
oxidative phosphorylation by increasing the demand for energy from ATP
hydrolysis beyond the capacity of cells to replenish ATP stores in a
timely manner. Excessive food intake and/or caffiene should, therefore,
increase the likelihood of developing an impairment of mitochondrial
oxidative phosphorylation especially in those with preexisting occlusive
vascular diseases.
There is a danger that in attributing adverse events, such as the
spontaneous loss of a pregnancy and ischaemic heart disease, to vascular
and haematologic disorders rather than to impaired mitochondrial oxidative
phosphorylation that detection of significant risk will be delayed and
accordingly management delayed, ineffective and/or even harmful.
1. Spontaneous loss of early pregnancy and risk of ischaemic heart
disease in later life: retrospective cohort study Gordon C S Smith, Jill P
Pell, and David Walsh BMJ 2003; 326: 423-424
2. Maternal consumption of coffee during pregnancy and stillbirth and
infant death in first year of life: prospective study Kirsten Wisborg,
Ulrik Kesmodel, Bodil Hammer Bech, Morten Hedegaard, and Tine Brink
Henriksen BMJ 2003; 326: 420
3. SIDS: identifying the real cause or causes Richard G Fiddian-Green
bmj.com/cgi/eletters/325/7371/981#27589, 5 Dec 2002
4. Neural tube defects and periconceptional folic acid in England and
Wales: retrospective study • Commentary: Food should be fortified with
folic acid Rezan A Kadir, Caroline Sabin, Barry Whitlow, Ely Brockbank,
Demetrios Economides, Eva Alberman, and Joan M Noble
BMJ 1999; 319: 92-93
5. On the beneficial effects of contaminants in folate supplements
Richard G Fiddian-Green bmj.com/cgi/eletters/326/7381/131#28861, 17 Jan
2003
6. "Lactic acidosis": the common denominator? Richard G Fiddian-Green
bmj.com/cgi/eletters/325/7374/1202#28322, 2 Jan 2003
7. Iatrogenic diseases with a common cause? Richard G Fiddian-Green
bmj.com/cgi/eletters/325/7370/913#26512, 25 Oct 2002
8. Madness, hyperhomocysteinemia, metabolic rate and body temperature
Richard G Fiddian-Green bmj.com/cgi/eletters/325/7378/1433#28469, 6 Jan
2003
9. Metformin, "lactic acidosis" and renal failure Richard G Fiddian-Green
bmj.com/cgi/eletters/326/7379/4#28486, 6 Jan 2003
10. Hypertension: product of mitochondrial dysfunction?
Richard G Fiddian-Green bmj.com/cgi/eletters/325/7370/917#26634, 31 Oct
2002
11. Unreversed ATP hydrolysis: the initiating endothelial event? Richard G
Fiddian-Green bmj.com/cgi/eletters/325/7369/887#26445, 22 Oct 2002
12. Hyperphosphataemia, hypophosphataemia and risk of organ dysfunctions
and failures Richard G Fiddian-Green
bmj.com/cgi/eletters/326/7385/382#29805, 20 Feb 2003
14. Determining the cause(s) of SIDS Richard G Fiddian-Green
bmj.com/cgi/eletters/325/7371/1007#29622, 13 Feb 2003
15. Hypophosphataemia and the feeding of malnourished children Richard G
Fiddian-Green bmj.com/cgi/eletters/326/7381/146#29382, 3 Feb 2003
Rapid Response:
Consequences of vascular or mitochondrial disorders?
The findings of an association between spontaneous abortion and
maternal risk of ischaemic heart disease (1) and that drinking coffee
during pregnancy is associated with an increased risk of stillbirth but
not with infant death (2) are consistent with the hypothesis that fetal
and infant wellness are dependent upon the adequacy of mitochondrial
oxidative phosphorylation (3). That some studies have shown that folate
supplements reduce the risk of neural tube defects and others have shown
that it does not (4) would also be consistent with this hypothesis if the
beneficial effects of the supplement were to be shown to be due to the
effects of the potent xanthine oxidase inhibitor contaminating commercial
preparations of folate rather than the folate per se (5). The findings are
also consistent with the hypothesis that an inadequacy of mitochondrial
oxidative phosphorylation is the principle cause of acute and chronic
organ dysfunctions and failures and nosocomial infections in adults (6-
12).
Occult cardiovascular, microvascular, or haemostatic dysfunction may
in themselves be the products of an impairment of mitochondrial oxidative
phosphorylation in the intima and/or media (10,11). It which case it is
likely to be an inadequacy of mitochondrial oxidative phosphoprylation
rather than vascular and haematologic diseases, as proposed (1), that
result in "pregnancy complications during reproductive years and in overt
cardiovascular disease in later life". As the occult cardiovascular,
microvascular, or haemostatic dysfunction may also impair oxygen delivery
to cells they may, however, be a secondary cause of an inadequacy of
oxidative phosphoprylation.
In future stusies all causes of an inadequacy of oxidative
phosphorylation need to be considered including the effects of food which
are not unlike the effects of phosphodiesterase inhibitors such as
caffiene (14,15). Both food and caffiene may cause a transient impairment
or transient increase in the severity of an impairment of mitochondrial
oxidative phosphorylation by increasing the demand for energy from ATP
hydrolysis beyond the capacity of cells to replenish ATP stores in a
timely manner. Excessive food intake and/or caffiene should, therefore,
increase the likelihood of developing an impairment of mitochondrial
oxidative phosphorylation especially in those with preexisting occlusive
vascular diseases.
There is a danger that in attributing adverse events, such as the
spontaneous loss of a pregnancy and ischaemic heart disease, to vascular
and haematologic disorders rather than to impaired mitochondrial oxidative
phosphorylation that detection of significant risk will be delayed and
accordingly management delayed, ineffective and/or even harmful.
1. Spontaneous loss of early pregnancy and risk of ischaemic heart
disease in later life: retrospective cohort study Gordon C S Smith, Jill P
Pell, and David Walsh BMJ 2003; 326: 423-424
2. Maternal consumption of coffee during pregnancy and stillbirth and
infant death in first year of life: prospective study Kirsten Wisborg,
Ulrik Kesmodel, Bodil Hammer Bech, Morten Hedegaard, and Tine Brink
Henriksen BMJ 2003; 326: 420
3. SIDS: identifying the real cause or causes Richard G Fiddian-Green
bmj.com/cgi/eletters/325/7371/981#27589, 5 Dec 2002
4. Neural tube defects and periconceptional folic acid in England and
Wales: retrospective study • Commentary: Food should be fortified with
folic acid Rezan A Kadir, Caroline Sabin, Barry Whitlow, Ely Brockbank,
Demetrios Economides, Eva Alberman, and Joan M Noble
BMJ 1999; 319: 92-93
5. On the beneficial effects of contaminants in folate supplements
Richard G Fiddian-Green bmj.com/cgi/eletters/326/7381/131#28861, 17 Jan
2003
6. "Lactic acidosis": the common denominator? Richard G Fiddian-Green
bmj.com/cgi/eletters/325/7374/1202#28322, 2 Jan 2003
7. Iatrogenic diseases with a common cause? Richard G Fiddian-Green
bmj.com/cgi/eletters/325/7370/913#26512, 25 Oct 2002
8. Madness, hyperhomocysteinemia, metabolic rate and body temperature
Richard G Fiddian-Green bmj.com/cgi/eletters/325/7378/1433#28469, 6 Jan
2003
9. Metformin, "lactic acidosis" and renal failure Richard G Fiddian-Green
bmj.com/cgi/eletters/326/7379/4#28486, 6 Jan 2003
10. Hypertension: product of mitochondrial dysfunction?
Richard G Fiddian-Green bmj.com/cgi/eletters/325/7370/917#26634, 31 Oct
2002
11. Unreversed ATP hydrolysis: the initiating endothelial event? Richard G
Fiddian-Green bmj.com/cgi/eletters/325/7369/887#26445, 22 Oct 2002
12. Hyperphosphataemia, hypophosphataemia and risk of organ dysfunctions
and failures Richard G Fiddian-Green
bmj.com/cgi/eletters/326/7385/382#29805, 20 Feb 2003
14. Determining the cause(s) of SIDS Richard G Fiddian-Green
bmj.com/cgi/eletters/325/7371/1007#29622, 13 Feb 2003
15. Hypophosphataemia and the feeding of malnourished children Richard G
Fiddian-Green bmj.com/cgi/eletters/326/7381/146#29382, 3 Feb 2003
Competing interests:
None declared
Competing interests: No competing interests