Journal of Orthomolecular Medicine, 6(3-4): 144-46,
Case Report: Lysine/Ascorbate-Related Amelioration of Angina
It is gratifying to
report the first observation of the amelioration of effort angina by the use of
high-dose L-lysine and ascorbate in a man with severe coronary artery disease
(CAD). This regimen was based on the hypothesis that, in thrombotic
atherosclerosis, lipoprotein(a) [Lp(a)]‹ size-heterogeneous, LDL- like particles
d displaying independent risk activity for CAD ‹initiates plaque formation by
binding to fibrin in the damaged arterial wall. This postulated mechanism
correlates with the findings that apoliprotein(a) [apo(a)] has a striking
homology to plasminogen and the Lp(a) accumulates in atherosclerotic lesions in
the arteries of man (Rath et al., 1989)and the hypoascorbic guinea pig (Rath and
Pauling, 1990a, 1990b) and in occluded bypass venous grafts (Cushing et al.,
1989). It is hoped that the remarkable outcome in this single case will motivate
clinicians to examine the efficacy of lysine and ascorbate in additional cases
of refractory angina.
Coronary Heart Disease Case History
late April 1991, a biochemist National Science Medalist* with a familial trait
of CAD told me that he experiences effort angina, in spite of medication and
three coronary bypass operations. His father and a brother both died of CAD at
age 62 he had his first angina attack at age 38. Now aged 71, this biochemist
has fought CAD also by reducing risk factors (i.e., not smoking, exercising
moderately, and diet/ weight control‹134 Ibs. at 5'5"). His first operation in
1978 (two vein grafts and one LIMA graft) precipitated a second operation (a
parallel vein graft) five months later. Stripping of saphenous veins in the
first operation induced massive swelling, thrombi, and infection in his leg;
bilateral pulmonary emboli; and loss of patency in a vein graft. In 1987,
following an attack of unstable angina, he was hospitalized for coronary
angiography, adjustment of medications, and a Tl-stress test. A third operation
in April 1990 followed attacks of unstable angina, a small MI, and angiography
that revealed total occlusion of his right coronary artery and all bypass grafts
except for a patent LIMA graft. Unfortunately, this LIMA was lacerated while
freeing dense adhesions early in the third operation and required urgent
heart-lung bypass cannulation and vein-patch repair; additionally, three venous
grafts were made to left coronary arteries. The operation, which diminished but
did not eliminate effort angina, left him with 1.8 liters of left-sided pleural
effusate that was resistant to diuretics and tapping, and took 10 months to
resorb. Medication with beta-receptor and calcium-channel blockers and
lovastatin was reinstated; also, 325 mg of aspirin given initially was reduced
to 81 mg following bilateral eye hemorrhages and adhesions that impair his
peripheral vision. To this medication, he added 6 g of ascorbate (acid form), 60
mg CoQ-10; a multivitamin tablet with minerals; additional vitamins A, E and a
B-complex; lecithin; and niacin, on advice of his cardiologist to try to raise
his HDL level. Nevertheless, he still had to take nitroglycerin sublingually to
suppress angina during a daily two mile walk and when working in his yard. This
effort angina continued to worsen, imparting a feeling of impending doom that
was reinforced by his cardiologist's admonition during a check-up in March 1991
that a fifth angiographic test and a fourth bypass operation were no longer
options. Also, the saphenous veins from his groin regions and legs had all been
used for previous grafts.
Effect of the Addition of Lysine
this predicament and with his history of restenosis, I suggested that he
continue ascorbate and add 5 g of L-lysine daily (ca., six times the lysine
derived from dietary protein) to try to mitigate the atherosclerotic acitivity
of Lp(a). After reading the 1990 Rath and Pauling reports and their manuscript
titled "Solution to the puzzle of human cardiovascular disease", he began taking
I g of lysine in early May 1991 and reached 5 g (in divided doses eight hours
apart) by mid-June. In mid-July, his HDL was, as usual, a low 28 mg/dl. A
low-normal 0.9 mg/dl blood creatinine indicated that lysine could be increased,
if needed. He could now walk the same two miles and do yard work without angina
pain and wrote, "the effect of the lysine borders on the miraculous". By late
August, he cut up a tree with a chain saw, and in early September started
painting his house. By late September, possibly from over-exertion, he again
began to have angina symptoms during his walks, but after stopping strenuous
work and increasing lysine to 6 g [calculated to provide a peak 280,000 molar
excess in the blood over his then 6 mg/dl of Lp(a) to help compensate for the
relatively high dissociation constant of lysine-Lp(a)] these symptoms stopped
entirely by mid-October. His blood creatinine was still a normal 1.2 mg/dl. He
attributes his newfound wellbeing to the addition of lysine to his other
medications and vitamins. His wife and friends comment on his renewed vigor.
This severe case of restenosing CAD was a
difficult challenge to try to ameliorate by the addition of lysine. While a
positive effect was anticipated, lysine had not been tested for activity in
inhibiting or reversing Lp(a)-laden atherosclerotic plaques in hypoascorbemic
guinea pigs (Rath and Pauling, 1990b). However, it was known that Lp(a) binds to
lysine-Sepharose, immobilized fibrin and fibrinogen (Harpel et al., 1989); and
the epithelial-cell receptor for plasminogen ( Gonzalez-Gronow et al., 1989).
This binding specificity correlates with the genetic linkage on chromosome six
and striking homology of apo(a) and plasminogen‹highly conserved multiple
kringle-four domains, a kringle-five domain, and a protease domain (McLean et
al., 1987). Moreover, using the molecular evolutionary clock, the loss in
primates of the ability to synthesize ascorbate (Zuckerkandl and Pauling, 1962;
Rath and Pauling, 1990a) and acquisition of Lp(a) (Maeda et al., 1983) both
appear to have occurred about 40 million years ago. These observations and the
presence of Lp(a) in sclerotic arteries (Rath et al., 1989; Rath and Pauling,
1990b) and in venous grafts (Cushing et al., 1989) indicate that atherosclerosis
may be initiated by excess binding of Lp(a) to fibrin in vascular wall clots,
thus interfering with normal fibrinolysis by plasmin. This thrombogenic
activity, which is postulated to reside in plasmin-homologous domains of Lp(a),
may help to stabilize the damaged vascular wall, especially in ascorbate
deficiency (Scanu, Lawn, and Berg, 1991; Rath and Pauling, 1990a). Once bound to
fibrin, the LDL-like domain of Lp(a) could promote atheromas (Scanu, Lawn, and
Berg, 1991). In this scenario, high-dosage lysine could inhibit or reverse
plaque accretion by binding to Lp(a). Independently, lysine benefits the heart
as a precursor with methionine in the synthesis of L-carnitine, the molecule
that carries fat into mitochondria for the synthesis of adenosine triphosphate
(ATP) bond energy needed for muscular and other cellular activities (Cederblad
and Linstedt, 1976). While his intake of 60 mg of CoQ-10, also required for ATP
synthesis, prior to the addition of lysine improved his sense of wellbeing, it
did not suppress his angina. Ascorbate without lysine also did not ameliorate
angina, but it is needed as an antioxidant to protect the vascular wall against
peroxidative damage and in hydroxylation reactions both in the synthesis of
carnitine and in the conversion of procollagen to collagen (hydroxylation of
prolyl and Iysyl residues) (Myllyla et al., 1984) to strengthen the
extracellular matrix of the wall.
Whatever the pathomechanisms of
atherosclerosis, the addition of lysine to medications and vitamins, including
ascorbate, markedly suppressed angina pectoris in this intractable case of CAD.
While a single case is anecdotal, it is hoped that its remarkable success will
motivate clinicians to commence studies as soon as possible of the general
applicability of lysine and ascorbate in relieving angina pectoris, so as to
decrease greatly the amount of human suffering with less dependence on surgical
Footnote (p. 144) *The biochemist patient made a
major contribution to this report, but wishes anonymity.
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