Better Living Through Chemistry

I actually believe that the commonly used preservatives BHA and BHT are good for our health. I am not being willfully contrarian. The idea that anti-oxidants (preservatives) may prevent cancer and heart disease is almost conventional (although unproven last I checked). For some reason, it is widely believed (especially among non biologists) that this means that natural anti-oxidants such as vitamin E and vitamin C are healthy, but it is know that artificial anti-oxidants such as BHA and BHT are dangerous.

Lots of junk below. I will quote some especially interesting bits

[Cancer Research 44, 134-138, January 1, 1984]
© 1984 American Association for Cancer Research

Wasyl Sydor, Jr.2, Katherine F. Lewis and Chung S. Yang3

"Butylated hydroxyanisole (BHA) is a commonly used food additive with demonstrated inhibitory action against chemical carcinogenesis in animals."

Cardiovasc Res. 2007 Apr 1;74(1):169-79. Epub 2007 Jan 27.Click here to read Links
Butylated hydroxyanisole stimulates heme oxygenase-1 gene expression and inhibits neointima formation in rat arteries.

"BHA represents a potentially novel therapeutic agent in treating or preventing vasculoproliferative disease."

[Cancer Research 42, 1199-1204, April 1, 1982]

Effect of Butylated Hydroxyanisole, {alpha}-Angelica Lactone, and ß-Naphthoflavone on Benzo({alpha})pyrene:DNA Adduct Formation in Vivo in the Forestomach, Lung, and Liver of Mice
Y. M. Ioannou1, A. G. E. Wilson2 and M. W. Anderson3

The inhibition of BPDEI:DNA and BPDEII:DNA adduct formation by {alpha}-AL, BHA, and ß-NF is discussed in relation to similar studies where these compounds inhibited BP-induced neoplasia.


Dietary agents ... are thought to prevent cancer by enhancing elimination of chemical carcinogens. The present study shows that compounds of this group (benzyl isothiocyanate, allyl sulfide, dimethyl fumarate, butylated hydroxyanisole)

[snip]


If this occurs in vivo, diets high in such compounds could eliminate precancerous cells by apoptosis at time points well after initial exposure to chemical mutagens and carcinogens.



Intake of butylated hydroxyanisole and butylated hydroxytoluene and stomach cancer risk: results from analyses in the Netherlands Cohort Study

"A statistically non-significant decrease in stomach cancer risk was observed with increasing BHA and BHT intake"


OK now all the junk.
Lets go to google scholar.

google scholar Butylated AND hydroxyanisole AND health


Safety Assessment of Butylated Hydroxyanisole and Butylated Hydroxytoluene as Antioxidant Food Additives

G. M. Williamsa, *, M. J. Iatropoulosa and J. Whysnera
a Department of Pathology, New York Medical College, American Health Foundation Valhalla, New York, 10595, USA

Available online 10 January 2000.

Food and Chemical Toxicology
Volume 37, Issues 9-10, 10 September 1999, Pages 1027-1038

Abstract

Butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) are widely used antioxidant food additives. They have been extensively studied for potential toxicities. This review details experimental studies of genotoxicity and carcinogenicity which bear on cancer hazard assessment of exposure to humans. We conclude that BHA and BHT pose no cancer hazard and, to the contrary, may be anticarcinogenic at current levels of food additive use.

Actually 2nd hit is relevant too

Cancer Lett. 1995 Jun 29;93(1):49-54.Click here

Phenolic antioxidants: Health Protection Branch studies on butylated hydroxyanisole.
Iverson F.

Toxicology Research Division, Health Protection Branch, Ottawa, Ont.

Synthetic phenolic antioxidants have been added to foods for decades to retard the autooxidation of lipid that leads to rancidity. The major antioxidants, butylated hydroxytoluene (BHT) and butylated hydroxyanisole (BHA), are used in foods world wide. Recent studies suggest that BHA, and perhaps BHT, are carcinogenic to rodents. International efforts, including those at the HPB in Ottawa Canada, have helped place the results of the chronic rodent studies into perspective. It seems likely that the neoplastic effects observed at very high dietary levels of BHA and BHT occur only after effective biological defense mechanisms are overloaded. The renewed interest in the toxicity of phenols is beneficial to an understanding of the complex biological effects of naturally occurring phenolics, including reduction of the levels of reactive oxygen species that are associated with various disease states in an aging human population.

Intake of butylated hydroxyanisole and butylated hydroxytoluene and stomach cancer risk: results from analyses in the Netherlands Cohort Study

A. A. M. Botterweck1, Corresponding Author Contact Information, E-mail The Corresponding Author, H. Verhagen 2, †, R. A. Goldbohm3, J. Kleinjans4 and P. A. van den Brandt1

Accepted 17 October 1999. Available online 25 August 2000.

Abstract

Both carcinogenic and anticarcinogenic properties have been reported for the synthetic antioxidants butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT). The association between dietary intake of BHA and BHT and stomach cancer risk was investigated in the Netherlands Cohort Study (NLCS) that started in 1986 among 120,852 men and women aged 55 to 69 years. A semi-quantitative food frequency questionnaire was used to assess food consumption. Information on BHA or BHT content of cooking fats, oils, mayonnaise and other creamy salad dressings and dried soups was obtained by chemical analysis, a Dutch database of food additives (ALBA) and the Dutch Compendium of Foods and Diet Products. After 6.3 years of follow-up, complete data on BHA and BHT intake of 192 incident stomach cancer cases and 2035 subcohort members were available for case-cohort analysis. Mean intake of BHA or BHT among subcohort members was 105 and 351 μg/day, respectively. For consumption of mayonnaise and other creamy salad dressings with BHA or BHT no association with stomach cancer risk was observed. A statistically non-significant decrease in stomach cancer risk was observed with increasing BHA and BHT intake [rate ratio (RR) highest/lowest intake of BHA=0.57 (95% confidence interval (CI): 0.25–1.30] and BHT=0.74 (95% CI: 0.38–1.43). In this study, no significant association with stomach cancer risk was found for usual intake of low levels of BHA and BHT.

I'm honest and note this even if it is old

Journal of Nutrition Vol. 108 No. 11 November 1978, pp. 1858-1867
Copyright © 1978 by American Society for Nutrition
T
Vitamin E, Antioxidants and Lipid Peroxidation in Experimental Atherosclerosis of Rabbits1
Robert B. Wilson, Charles C. Middleton2 and Grace Y. Sun2

Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington 99164, and Sinclair Comparative Medicine Research Farm, University of Missouri, Columbia, Missouri 65201

The purpose of this study was to evaluate the effects of large amounts of dietary vitamin E and butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) in rabbits fed a low-cholesterol, atherogenic diet, and to seek for evidence of lipid peroxidation in the atherosclerotic lesions. Rabbits were fed a purified atherogenic diet, containing butter or the basal diet supplemented with either 1.0% of vitamin E or 0.1% each of BHA and BHT for periods up to 3 years; a negative control group was fed the basal diet with corn oil replacing butter. Aortic and coronary atherosclerosis were more frequent and extensive in rabbits fed either the basal diet or the basal diet supplemented with BHA and BHT than in rabbits fed either the basal diet supplemented with vitamin E or the negative control diet. Dietary vitamin E inhibited atherogenesis by preventing hypercholesterolemia. No evidence of lipid peroxidation was detected in the artieral lesions.

This is more recent Money quote "BHA represents a potentially novel therapeutic agent in treating or preventing vasculoproliferative disease."

: Cardiovasc Res. 2007 Apr 1;74(1):169-79. Epub 2007 Jan 27.Click here to read Links
Butylated hydroxyanisole stimulates heme oxygenase-1 gene expression and inhibits neointima formation in rat arteries.
Liu XM, Azam MA, Peyton KJ, Ensenat D, Keswani AN, Wang H, Durante W.

Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO 65212, USA.

OBJECTIVE: Butylated hydroxyanisole (BHA) is a synthetic phenolic compound that is a potent inducer of phase II genes. Since heme oxygenase-1 (HO-1) is a vasoprotective protein that is upregulated by phase II inducers, the present study examined the effects of BHA on HO-1 gene expression and vascular smooth muscle cell proliferation. METHODS: The regulation of HO-1 gene expression and vascular cell growth by BHA was studied in cultured rat aortic smooth muscle cells and in balloon injured rat carotid arteries. RESULTS: Treatment of cultured smooth muscle cells with BHA stimulated the expression of HO-1 protein, mRNA and promoter activity in a time- and concentration-dependent manner. BHA-mediated HO-1 expression was dependent on the activation of NF-E2-related factor-2 by p38 mitogen-activated protein kinase. BHA also inhibited cell cycle progression and DNA synthesis in an HO-1-dependent manner. In addition, the local perivascular delivery of BHA immediately after arterial injury of rat carotid arteries induced HO-1 protein expression and markedly attenuated neointima formation. CONCLUSIONS: These studies demonstrate that BHA stimulates HO-1 gene expression in vascular smooth muscle cells, and that the induction of HO-1 contributes to the antiproliferative actions of this phenolic antioxidant. BHA represents a potentially novel therapeutic agent in treating or preventing vasculoproliferative disease.

an article translated from Slovak (give me a break you have your own country but you share a language with the Czecks)

"The protective effect of butylhydroxyanisole was demonstrated to be statistically significant in the examination of the extent of atheromatous changes in arterioles."
Alzheimer's

J Alzheimers Dis. 2008 Feb;13(1):31-8.Click here to read Links
Nutritional Biomarkers in Alzheimer's Disease: The Association between Carotenoids, n-3 Fatty Acids, and Dementia Severity.
Wang W, Shinto L, Connor WE, Quinn JF.

Department of Medicine, Oregon Health and Science University, Portland, OR 97239, USA.

Carotenoids are fat-soluble antioxidants that may protect polyunsaturated fatty acids, such as n-3 fatty acids from oxidation, and are potentially important for Alzheimer's disease (AD) prevention and treatment.

[snip]

These findings suggest targeting multiple specific nutrients, lutein, beta-carotene, and DHA in strategies to slow the rate of cognitive decline.

CNS Neurol Disord Drug Targets. 2008 Feb;7(1):3-10.Click here to read Links
Alzheimer disease and the role of free radicals in the pathogenesis of the disease.
Moreira PI, Santos MS, Oliveira CR, Shenk JC, Nunomura A, Smith MA, Zhu X, Perry G.

College of Sciences, University of Texas at San Antonio, San Antonio, Texas 78249, USA. george.perry@utsa.edu.

Oxidative stress occurs early in the progression of Alzheimer disease, significantly before the development of the pathologic hallmarks, neurofibrillary tangles and senile plaques.

So what about carcinogenisis

Food Chem Toxicol. 1994 Mar;32(3):215-22.Click here to read Links
Dose response of promotion by butylated hydroxyanisole in chemically initiated tumours of the rat forestomach.
Whysner J, Wang CX, Zang E, Iatropoulos MJ, Williams GM.

Division of Pathology and Toxicology, American Health Foundation, Valhalla, NY 10595.

The antioxidant food preservative butylated hydroxyanisole (BHA) was tested in an initiation-promotion protocol in which male F344 rats (6 wk old), 27 per group, were gavaged with a single dose of 200 mg N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)/kg. After 3 wk on control diet, test diets containing 0, 60, 300, 1000, 3000, 6000 or 12,000 ppm BHA were fed until termination of the experiment at approximately 110 wk, at which time most animals had died with stomach tumours. MNNG caused a high incidence of tumours in the glandular stomach and forestomach of all groups. Administration of 12,000 and 6000 ppm BHA, but not 3000 ppm or lower doses, caused statistically significant increases in the time-related incidence of MNNG-induced forestomach tumours as analyzed by life table analysis. BHA had no effect on the incidence of tumours in the glandular stomach or oesophagus. Tumour incidences in other organs were not related to BHA dose. No increase in hyperplasia in the oesophagus was evident in the high-dose BHA-treated animals compared with the MNNG-only group. This study provides corroboration that BHA affects only forestomach tumorigenesis and that the dose for enhancement of tumorigenesis is at least 1500-fold greater than human exposure.

hah

also

Cancer Research 49, 1357-1360, March 15, 1989]
© 1989 American Association for Cancer Research

Effect of Butylated Hydroxyanisole Pretreatment on Aflatoxin B1-DNA Binding and Aflatoxin B1-Glutathione Conjugation in Isolated Hepatocytes from Rats1
Eun-Chung Jhee2, Ling Ling Ho, Kojiro Tsuji, Prathima Gopalan and Prabhakar D. Lotlikar3

"It appears that the induced cytosolic GSH S-transferases after BHA treatment of rats play a significant role in inhibiting hepatic AFB1-DNA binding and AFB1 hepatocarcinogenesis presumably by inactivation of the reactive AFB1-epoxide."


[Cancer Research 44, 134-138, January 1, 1984]
© 1984 American Association for Cancer Research

Wasyl Sydor, Jr.2, Katherine F. Lewis and Chung S. Yang3

Department of Biochemistry, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07103

Butylated hydroxyanisole (BHA) is a commonly used food additive with demonstrated inhibitory action against chemical carcinogenesis in animals. In order to elucidate the mechanism of the anticarcinogenic action, the effects of BHA on benzo(a)pyrene (BP) metabolism were studied with lung microsomes from female mice. BHA treatment (0.5% in the diet for 7 days) inhibited BP metabolism and altered the ratios among different metabolites as analyzed by high-performance liquid chromatography. The treatment reduced the metabolic formation of 9,10-dihydroxy-9,10-dihydrobenzo(a)pyrene, but not the production of 3-hydroxybenzo(a)pyrene and trans-4,5-dihydroxy-4,5-dihydrobenzo(a)pyrene. Since the gross microsomal cytochrome P-450 content was not significantly affected by the treatment, the change of regioselectivity in BP metabolism was probably due to the alteration of cytochrome P-450 isozyme composition by dietary BHA. General and regioselective inhibition of BP metabolism was also observed when BHA was added to the lung microsomal incubation mixture. The formation of 9,10-dihydroxy-9,10-dihydrobenzo(a)pyrene and 9-hydroxybenzo(a)pyrene was inhibited more severely than that of trans-4,5-dihydroxy-4,5-dihydrobenzo(a)pyrene and trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene, but the production of 3-hydroxybenzo(a)pyrene was not inhibited. Dietary BHA treatment also decreased the microsomal metabolism of trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene to n-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene and r-7,t-8-dihydroxy-c-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene. Considering that the former diol-epoxide is a suspected ultimate carcinogen, the observed inhibitions of BP metabolism in the formation of diolepoxides may be closely related to the anticarcinogenic action of BHA.

1 This work was supported by Grant CA-28298 from the National Cancer Institute.

2 Present address: Roche Institute of Molecular Biology, Nutley, N. J. 07110.


(Journal of Nutrition. 1999;129:1827-1835.)
Dietary Compounds That Induce Cancer Preventive Phase 2 Enzymes Activate Apoptosis at Comparable Doses in HT29 Colon Carcinoma Cells1
Ward G. Kirlin*,{dagger}, Jiyang Cai*, Mary J. DeLong**,{ddagger}, Emma J. Patten**,{ddagger} and Dean P. Jones*,{ddagger}2



Dietary agents that induce glutathione S-transferases and related detoxification systems (Phase 2 enzyme inducers) are thought to prevent cancer by enhancing elimination of chemical carcinogens. The present study shows that compounds of this group (benzyl isothiocyanate, allyl sulfide, dimethyl fumarate, butylated hydroxyanisole) activated apoptosis in human colon carcinoma (HT29) cells in culture over the same concentration ranges that elicited increases in enzyme activity (5–25, 25–100, 10–100, 15–60 µmol/L, respectively). Pretreatment of cells with sodium butyrate, an agent that induces HT29 cell differentiation, resulted in parallel increases in Phase 2 enzyme activities and induction of apoptosis in response to the inducers. Cell death characteristics included apoptotic morphological changes, appearance of cells at sub-G1 phase on flow cytometry, caspase activation, DNA fragmentation and TUNEL-positive staining. The results suggest that dietary Phase 2 inducers may protect against cancer by a mechanism distinct from and in addition to that associated with enhanced elimination of carcinogens. If this occurs in vivo, diets high in such compounds could eliminate precancerous cells by apoptosis at time points well after initial exposure to chemical mutagens and carcinogens.