Fruit and vegetable intake and incidence of type 2 diabetes mellitus: systematic review and meta-analysis
BMJ 2010; 341 doi: https://doi.org/10.1136/bmj.c4229 (Published 19 August 2010) Cite this as: BMJ 2010;341:c4229
All rapid responses
Sirs:
The new meta-analysis by Carter et al.(1) confirms previous
epidemiological evidence linking diets rich in green leafy vegetables - as
opposed to fruits and vegetables overall - to reduced risk for type 2
diabetes. Consideration should be given to the possibility that this
likely protection is mediated by the high nitrate content of green leafy
vegetables.(2) Recent research establishes that dietary nitrate can give
rise to plasma nitrite that in turn can be reduced to nitric oxide (NO),
independent of NO synthase activity.(3) In rodent skeletal muscle, NO has
been shown to activate AMPK, boost expression of GLUT4, and promote
mitochondrial biogenesis - all effects that should be conducive to good
insulin sensitivity.(4-6) Rodent and clinical studies should evaluate the
impact of dietary nitrate on insulin sensitivity and glycemic control.
Sincerely, Mark F. McCarty, markfmccarty@gmail.com
References
(1) Carter P, Gray LJ, Troughton J, Khunti K, Davies MJ. Fruit and
vegetable intake and incidence of type 2 diabetes mellitus: systematic
review and meta-analysis. BMJ 2010; 341:c4229.
(2) Hord NG, Tang Y, Bryan NS. Food sources of nitrates and
nitrites: the physiologic context for potential health benefits. Am J Clin
Nutr 2009; 90(1):1-10.
(3) Webb AJ, Patel N, Loukogeorgakis S, Okorie M, Aboud Z, Misra S
et al. Acute blood pressure lowering, vasoprotective, and antiplatelet
properties of dietary nitrate via bioconversion to nitrite. Hypertension
2008; 51(3):784-790.
(4) Lira VA, Soltow QA, Long JH, Betters JL, Sellman JE, Criswell
DS. Nitric oxide increases GLUT4 expression and regulates AMPK signaling
in skeletal muscle. Am J Physiol Endocrinol Metab 2007; 293(4):E1062-
E1068.
(5) Nisoli E, Falcone S, Tonello C, Cozzi V, Palomba L, Fiorani M et
al. Mitochondrial biogenesis by NO yields functionally active mitochondria
in mammals. Proc Natl Acad Sci U S A 2004; 101(47):16507-16512.
(6) Wadley GD, McConell GK. Effect of nitric oxide synthase
inhibition on mitochondrial biogenesis in rat skeletal muscle. J Appl
Physiol 2007; 102(1):314-320.
Competing interests:
None declared
Competing interests: No competing interests
Carter and colleagues’ systematic review and meta-analysis
demonstrated that a diet rich in green, leafy vegetables but not fruit and
vegetables or “vegetables” may confer protection against the risk of
developing type 2 diabetes mellitus[1]. They attribute this protective
effect to the possible role of a variety of antioxidants. A diet rich in
fruit and vegetables would seem to increase consumption of these
antioxidants however does not confer the same degree of protection as that
from a diet rich in green leafy vegetables. A similar result was reported
by Jae et al during a prospective study examining rates of cognitive
decline[2]. Again green leafy vegetables were protective where other
dietary components were not. The green leafy vegetables described (eg
spinach, kale, lettuce,) differ from fruits and other vegetables in one
important way--all have a high nitrate content[3]. Nitrate from the diet
has been shown to have numerous beneficial physiological effects[4]
including lowering blood pressure[5], improving endothelial function, and
protecting against ischaemia reperfusion injury. Dietary nitrate is now
known to be metabolised in humans to nitric oxide by sequential bacterial
and chemical reduction[6], and may be able to restore deficient levels
which have been postulated to mediate the genesis and consequences of type
2 diabetes[7]. It is possible that the protective effect seen in the
present analysis is a consequence of the vascular actions of nitrate from
the diet.
1. Carter, P., et al., Fruit and vegetable intake and incidence of
type 2 diabetes mellitus: systematic review and meta-analysis. BMJ, 2010.
341(aug18_4): p. c4229-.
2. Jae, H.K., A. Alberto, and G. Francine, Fruit and vegetable
consumption and cognitive decline in aging women. Annals of Neurology,
2005. 57(5): p. 713-720.
3. Nitrate in Vegetables. 1998, MAFF UK.
4. Gilchrist, M., P.G. Winyard, and N. Benjamin, Dietary nitrate -
Good or bad? Nitric Oxide, 2010. 22(2): p. 104-109.
5. Webb, A.J., et al., Acute blood pressure lowering, vasoprotective, and
antiplatelet properties of dietary nitrate via bioconversion to
nitrite.Hypertension, 2008. 51(3): p. 784-90.
6. Lundberg, J.O., et al., Nitrate, bacteria and human
health.[erratum appears in Nat Rev Microbiol. 2004 Aug;2(8):681]. Nature
Reviews, 2004. Microbiology. 2(7): p. 593-602.
7. Scherrer, U. and C. Sartori, Defective nitric oxide synthesis: a
link between metabolic insulin resistance, sympathetic overactivity and
cardiovascular morbidity. Eur J Endocrinol, 2000. 142(4): p. 315-323.
Competing interests:
Professor Nigel Benjamin is a cofounder of Heartbeet Ltd, a non-profit making organisation set up to promote the health benefits of dietary nitrate
Competing interests: No competing interests
Public health implications versus individual benefits
Carter and colleagues found that eating 1.35 servings a day of green
leafy vegetables was associated with a 14% risk reduction for type 2
diabetes compared with 0.2 servings. The authors conclude that increasing
the daily intake of green leafy vegetables could significantly reduce the
incidence of type 2 diabetes.
It is important to differentiate between the public health
implications and individual benefits.
In the Finnish Diabetes Prevention Study, the annualised incidence
rate of diabetes was 6% in a group of high risk individuals with impaired
glucose tolerance (1). A 15% reduction sounds impressive but the actual
impact of eating an extra portion of green leafy vegetables in this high
risk population would reduce the incidence of diabetes by 0.9%.
Consequently the numbers needed to treat to prevent one case of diabetes
would have been 112.
Thus an emphasis on relative measures of decreased risk may lead to
undue confidence in the benefit of green leafy vegetables to prevent type
2 diabetes. For individuals not at high risk for developing diabetes, the
numbers needed to treat would be even higher, and thus even less
important.
By contrast, as a public health measure, a policy advocating
increased green leafy vegetables may pay dividends. With approximately
250,000 new cases of diabetes every year in the UK, a 15% reduction by
eating an extra portion of green leafy vegetables may mean that nearly
40,000 fewer people develop diabetes.
This critique does not take into account the many other benefits of
green leafy vegetables; after all many decades ago, Popeye discovered
the advantage of a high spinach diet!
Richard IG Holt
Professor in Diabetes and Endocrinolgy
University of Southampton
righ@soton.ac.uk
Les Citrome
Professor of Psychiatry
Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York,
USA.
citrome@nki.rfmh.org
1.Tuomilehto J, Lindstrom J, Eriksson JG et al. Prevention of type 2
diabetes mellitus by changes in lifestyle among subjects with impaired
glucose tolerance N Engl J Med. 2001 May 3;344(18):1343-50
Competing interests: No competing interests