April 28, 2004
Kathryn
McMurry
HHS Office of Disease Prevention and Health Promotion
Room 738-G
200 Independence Avenue, SW
Washington, D.C. 20201
Dear
Kathryn:
The April 26 Federal Register indicated that the final
deadline to get further comments to the Dietary Guidelines Advisory Committee has been
extended until May 12 permitting these further comments. While our basic objection
to having a Guideline for salt/sodium is that there is no evidence that reducing dietary
sodium improves health outcomes, a recent article suggests a new concern for the potential
risk of reducing salt intakes: the study suggests that low-salt diets create salt
sensitivity.
The DGAC had a short discussion about the question of salt
sensitivity and how we now understand that this is a modifiable risk factor. We maintain that a proper focus of nutrition
advice might be more properly understood as an effort to prevent salt sensitivity rather
than reduce salt intake. I would remind you
of the article by A.G. Logan making this point as noted in my earlier letter. Publication of this study adds still another
caution to the course charted by the 2000 Guidelines and proposed by sub-committee chair
Larry Appel.
The
review article to which I refer appeared in the March 21 issue of the New England
Journal of Medicine, entitled “Subtle acquired renal injury as a mechanism of
salt-sensitive hypertension;” it was authored by Richard J. Johnson, et al. (NEJM
2002 Mar 21; 346(12):913-923).
What
is interesting – and relevant for the DGAC – is that in experimental models, a
potentially nephrotoxic agent or biological exerted its adverse effects only when the
animals were consuming a low-salt diet; on a normal salt diet the adverse effects did not
occur. Johnson et al reviewed the literature finding on the problematic renal
impacts of elevated plasma renin activity, hyperactivity of the sympathetic nervous system
(both effects my earlier letters have noted are the result of sodium restriction) and use
of cyclosporine. In particular, the DGAC
would do well to review one of the studies quoted: that of T.F. Andoh and Bill Bennett et
al that examined how cyclosporine induced renal injury; that article appeared in the American
Journal Transplantation. 2001 Sep;1(3):222-227.
The
identified renal injury was subtle – a microvascular and tubulointerstital injury.
Importantly it did not lead to any change in renal function as measured by normal blood
tests, serum creatinine, as in the early stages such common clinical tests would not
detect the type of tubulo-interstitial injury noted. The authors identified acute renal
vasoconstriction as the cause. What I would
particularly highlight for the DGAC is that after the injury the animals had normal
blood pressure on a low salt diet, but became hypertensive on a high salt diet.
Johnson et al confirmed that afferent arteriolopathy was responsible for creating
this salt sensitivity by affecting the blood vessels, particularly the diameter of the
lumina, which “can markedly reduce blood flow and increase vascular resistance.” The authors say it best:
In summary, we suggest that in many cases of hypertension, the kidney is initially normal but undergoes subclinical injury over time, leading to the development of afferent arteriolopathy (arteriolosclerosis) and tubulointerstitial disease. The initiation of renal injury may be induced by hyperactivity of the sympathetic nervous system, by inappropriate activation or overstimulation of the renin-angiotensin system, or by any factor that causes renal vasoconstriction (such as hypokalemia or the use of cyclosporine).
And, they continued, “With
continued vasoconstriction, afferent arteriolopathy develops, impairing blood flow and
causing persistent renal ischemia.” This,
they say, explains why salt sensitivity increases with aging. Stated somewhat more simply,
with the original injury induced in part by a restricted sodium diet, renal function can
no longer maintain the sodium excretory capacity. When the kidneys are then presented with
a normal sodium diet, volume expansion occurs and blood pressure increases. The animal or
the human would be labeled “salt sensitive.”
In fact, though, the salt sensitivity is the result of a low sodium diet.
The
public health implications of these findings could be enormous. The advice of the
current salt Guideline may be responsible for creating among those who follow it the
subtle renal injury identified in this study and producing the salt sensitivity that is an
identified risk factor for CV events. As this
study shows, it is likely that individuals on a low salt diet will be more vulnerable to
developing subclinical renal injury from everyday events including many commonly used
over-the-counter and prescription drugs. These subtle injuries will predispose them to
develop salt-sensitive hypertension in the future. This risk would be particularly
troublesome for the older population. They experience a natural decline in renal function
with age. A low sodium diet would simply increase that risk. Furthermore they are the
subjects most likely to adhere to a lower sodium diet. Individuals on a normal salt
diets will not be as vulnerable. One example given in the NEJM article was a that a
chronic low potassium diet (common in blacks) induces subtle renal injury.
There
is a substantial body of experimental literature supporting this view. This study offers valuable insight into the
particular vulnerability documented among African-Americans, older Americans and Americans
consuming inadequate amounts of calcium, potassium and magnesium. It is consistent with the salutary effects of the
DASH Diet that corrects these electrolyte deficiencies.
Nephrologists
– and FDA regulators—clearly understand the use of ACE inhibitors to preserve
renal function and slow the progression of disease, as well as preserve cardiac function.. Presumably, then, it follows that these experts
understand that low sodium diets, which induce the reverse physiologic effect, i.e. volume
constriction and the attendant increase in the renin-angiotensin system, cannot be good
for the kidney. After all, the HOPE Trial, using this rationale, suggests that heart
failure and stokes are a very real potential outcome of low-sodium diets. Does it not
strike anyone as inconsistent that the government has been promoting the use of ACE
inhibitors to improve CV outcomes while also promoting low-sodium diets? Does it make any physiological sense??
The
DGAC is one of the infrequent opportunities for scientists to look squarely at the
scientific evidence and say “the emperor has no clothes.”
There
should be no Guideline for salt. We urge the
DGAC to provide food-based guidelines to eliminate mineral deficiencies and follow sound
science.
Sincerely,
Richard
L. Hanneman
President
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