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RESEARCH: Ioanna Tzoulaki, Ian J Brown, Queenie Chan, Linda Van Horn, Hirotsugu Ueshima, Liancheng Zhao, Jeremiah Stamler, Paul Elliott for the International Collaborative Research Group on Macro-/Micronutrients and Blood Pressure Relation of iron and red meat intake to blood pressure: cross sectional epidemiological study BMJ 2008; 337: a258 [Abstract] [Full text]

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The 4 H Hypothesis

SUJOY GHOSH, James Rose, Andrew Collier, Iqbal Malik   (29 July 2008)

Prospective controlled research on red meat, haem iron, and blood pressure

Janet R Hunt   (4 August 2008)

Question re: type of beef used in studies

Margaret M. Shockley   (2 February 2009)

The 4 H Hypothesis 29 July 2008
SUJOY GHOSH, Clinical Teaching & Clinical Research Fellow The Ayr Hospital, Dalmellington Road, Ayr, KA6 6DX, James Rose, Andrew Collier, Iqbal Malik Send response to journal: Re: The 4 H Hypothesis	We have read with interest the article by Tzoulaki et al. and the accompanying editorial. [1, 2] Recent studies have suggested that even moderately raised iron stores and plasma ferritin concentrations, below those seen in haemochromatosis, may induce insulin resistance, hyperinsulinaemia, diabetes and the metabolic syndrome. [3] We also know that hypertension is more prevalent amongst obese subjects or in patients with diabetes, i.e. in subjects with hyperinsulinaemia and insulin resistance. [4] Longitudinal studies have demostrated that insulin resistance may precede the development of frank hypertension [5] and it is thought that the hyperinsulinaemia activates the adrenergic nervous system. [6] The findings of the study by Tzoulaki et al. suggest that haem iron intake from food is positively associated with a non-statistical rise in systolic and diastolic blood pressure. The raised haem iron intake seems to alter iron metabolism possibly through changes in oxidative stress leading to an increase in insulin resistance and hyperinsulinaemia [7].Hence we hypothesise that excess haem iron intake leads to hyperferritinaemia and hyperinsulinaemia which in turn could lead to hypertension – our 4H-hypothesis. REFERENCES: [1] Tzoulaki I, Brown IJ, Chan Q, Van Horn L, Ueshima H, Zhao L, Stamler J, Elliott P; International Collaborative Research Group on Macro- /Micronutrients and Blood Pressure. Relation of iron and red meat intake to blood pressure: cross sectional epidemiological study. BMJ. 2008 Jul 15; 337 [2] Stranges S, Guallar E. Dietary iron and blood pressure. BMJ. 2008 Jul 15; 337 [3] Jehn ML, Guallar E, Clark JM, Couper D, Duncan BB, Ballantyne CM, Hoogeveen RC, Harris ZL, Pankow JS. A prospective study of plasma ferritin level and incident diabetes: the Atherosclerosis Risk in Communities (ARIC) Study. Am J Epidemiol. 2007 May 1; 165(9):1047-54. [4] Ferrannini E. The phenomenon of insulin resistance: its possible relevance to hypertensive disease. In: Laragh JH, Brenner BM, eds. Hypertension: Pathophysiology, Diagnosis and Management, 2nd Ed. New York, NY: Raven Press; 1995: 2281-2300. [5] Haffner SM, Miettinen H, Gaskill SP, Stern MP. Metabolic precursors of hypertension. The San Antonio Heart Study. Arch Intern Med. 1996 Sep 23; 156(17):1994-2001. [6] Ferrannini E, Buzzigoli G, Bonadonna R, Giorico MA, Oleggini M, Graziadei L, Pedrinelli R, Brandi L, Bevilacqua S. Insulin resistance in essential hypertension. N Engl J Med. 1987 Aug 6;317(6):350-7. [7] Jehn HL, Guallar E, Clark JM, Couper D, Duncan BB, Ballantyne CM et al. A prospective study of plasma ferritin and level and incident diabetes:the atherosclerosis risk in communities (ARIC) study. Am J Epidemiol 2007; 165:1047-54 Competing interests: None declared
Prospective controlled research on red meat, haem iron, and blood pressure 4 August 2008
Janet R Hunt, Research Nutritionist USDA-ARS Grand Forks Human Nutrition Research Center, Grand Forks, ND 58202 Send response to journal: Re: Prospective controlled research on red meat, haem iron, and blood pressure	The recent report of Tzoulaki and colleagues [1] on a large cross- sectional epidemiological international collaborative study on macro- /micronutrients and blood pressure (INTERMAP) indicated that blood pressure was negatively associated with non-haem iron ingestion and positively associated with red meat intake. Both this paper and the accompanying editorial noted the need for confirmation of such findings with prospective controlled studies. I am writing to draw attention to a relevant small, but well-controlled prospective study from our laboratory. We reported no change in the systolic or diastolic resting blood pressure of 21 healthy premenopausal women who consumed weighed experimental lacto-ovo-vegetarian and meat-containing diets (with equivalent food energy) for 8 wk each in a randomized cross-over design [2]. These two diets contained 0 and 184 g meat/d, respectively. Three- quarters of this meat was beef, with chicken as the remainder. As described in a subsequent paper emphasizing iron content and absorption/bioavailability [3], the two diets contained 12.6 and 13.6 mg total iron, and 0 and 1.2 mg haem iron/d, respectively. Compared to the meat-containing diet, the lacto-ovo-vegetarian diet resulted in substantially lower non-haem and total iron absorption [3]. This small study with controlled diets for 8 wk each does not support a positive association of red meat or haem iron intake with blood pressure, under conditions of equivalent energy consumption. REFERENCES [1] Tzoulaki I, Brown IJ, Chan Q, Van Horn L, Ueshima H, Zhao L, et al. Relation of iron and red meat intake to blood pressure: cross sectional epidemiological study. Bmj 2008;337:a258. [2] Hunt JR, Matthys LA, Johnson LK. Zinc absorption, mineral balance, and blood lipids in women consuming controlled lactoovovegetarian and omnivorous diets for 8 wk. Am J Clin Nutr 1998;67:421-430. [3] Hunt JR, Roughead ZK. Nonheme-iron absorption, fecal ferritin excretion, and blood indexes of iron status in women consuming controlled lactoovovegetarian diets for 8 wk. Am J Clin Nutr 1999;69:944-52. Competing interests: Author has received some research funding from the National Cattlemen's Beef Association in the USA.
Question re: type of beef used in studies 2 February 2009
Margaret M. Shockley, Nutrtitional Counselor East West Healing Arts Center, 751 Holton Road, Talent, OR 97540 Send response to journal: Re: Question re: type of beef used in studies	I am interested to know if any research on the relationship of beef intake to hypertensive states has addressed the differences between consumption of grain-fed vs. grass-fed beef i.e., does the type of fat and protein formed by the animal's feed have any correlation to the meat's impact on blood pressure readings. Competing interests: None declared