For the past year or more, I have been asked about whether it is safe to take multivitamins with copper because of a fear that is apparently spreading. The fear is that 1-2 mg of copper in multivitamins supposedly causes dementia and/or Alzheimer's disease.
The rumor appears to be based on statements made in two recently published commentaries by Brewer,1-2 who says to "check your multi-vitamin mineral pill (or any other supplement pills) and see if it contains copper. If it does, throw it out."2 Most multivitamin / mineral supplements contain 1-2 mg of copper.
If Brewer is correct, then how could people with mild Alzheimer's disease take 8 mg of copper daily for 12 months and not have greater Alzheimer's progression than placebo?3 And moreover, if it were so obvious that 1-2 mg of supplemental copper caused dementia / Alzheimer's, why would researchers give 8 mg per day for 12 months straight?
The reason for supplementing Alzheimer's patients with copper is because researchers identified that copper deficiency might be a cause of Alzheimer's,4 so they compared 8 mg of supplemental copper per day with placebo. The outcome was that the rate of progression was identical between groups.3 Surely if a 1-2 mg of copper in a multivitamin / mineral causes Alzheimer's in people without Alzheimer's, then 8 mg would make it worse in those already compromised. Additionally, there were no toxic side effects identified in the group supplemented with 8 mg of copper.
The fact that 8 mg per day of supplemental did not increase Alzheimer's expression is not surprising, as the upper tolerable limit for copper ingestion is set at 10 mg per day.5 In fact, "copper toxicity is rather rare in humans and animals, because mammals have evolved precise homeostatic control of copper due to the high reactivity of the free metal."5 Free copper in cells and in circulation always exists in low concentrations and is primarily bound to proteins.5 However, a chronic excess of free copper, like iron, leads to the overproduction of free radicals.
Alzheimer's and Type 2 Diabetes
With the above in mind, studies have identified that circulating free copper is elevated patients with Alzheimer's disease.1-2 Interestingly, copper is also elevated in patients with type 2 diabetes.6-9 Are we to leap to the conclusion that copper causes Alzheimer's and type 2 diabetes? No; that is also the wrong conclusion.
However, if one were to leap to that conclusion, you can see why one might conclude that the "copper sky is falling" and we should all stop taking multivitamins lest we rapidly succumb to dementia. This would be akin to avoiding water consumption because in excess, as in drowning, water can kill you – clearly an absurd assumption. Instead of blaming copper, we should investigate why copper can be elevated in patients with Alzheimer's and diabetes.
Serum Copper Normally Elevates With Inflammation
It should be understood that both Alzheimer's and type 2 diabetes are caused by chronic inflammation.10 Alzheimer's and diabetes are quite similar in that amyloid deposition is common to each.11 Oxidative stress has been identified as a common pathophysiologic mechanism in both Alzheimer's and type 2 diabetes.11 Oxidative stress is part of the inflammatory state; I described this relationship in an MPA webinar a few years ago.12 This is worth watching because it explains how oxidative stress / inflammation are generated by an inflammatory diet.
It appears that circulating copper levels increase in a fashion commensurate with a patient's degree of chronic inflammation. By 1991, researchers knew serum copper levels were elevated in patients with diabetic complications, lymphocytic leukemia, inflammation, atherosclerosis, and hypertension in the absence of diabetes.6 So, elevated copper levels in Alzheimer's patients should not be a surprise.
Even earlier, in 1985, researchers identified that "serum copper and/or ceruloplasmin act as acute-phase reactants in vascular disease, inflammation, and malignancy."13 In other words, copper normally elevates in these conditions, independent of copper intake.
Additional acute-phase reactants include ferritin, hsCRP and serum amyloid A. They all normally rise during acute inflammatory events, such as in an infection, and then fall just as rapidly back to normal. When they stay elevated, it is because a chronic inflammatory state exists. Type 2 diabetes is an example of such a state.
Hyperglycemia, as measured by hemoglobin A1c (HbA1c), is correlated to hsCRP levels.14 And emergent type 2 diabetes appears to correlate with rising levels of hsCRP.15 Similarly, as glycemic control worsens, serum copper levels can rise accordingly.8
Practical Applications
We know chronic excess of serum copper and iron can generate free radicals. So, the goal should be to avoid chronic inflammation, which is caused by the regular consumption of refined carbohydrates, omega-6 fatty acids and trans fats.
Interestingly, higher levels of copper consumption may be linked to cognitive decline in subjects eating a pro-inflammatory diet, but not in those with an anti-inflammatory diet.16 So, it is not an issue of dietary or supplemental "copper"; it is about the patient's inflammatory state. I recently wrote three papers that contain lists of inflammatory markers that can be readily identified in clinical practice.17-19
According to the available evidence, if we avoid pro-inflammatory foods and maintain proper glycemic control, 1-2 mg of copper in a multivitamin / mineral will have absolutely no effect on cognitive function. Fears about this relationship are unfounded and should be abandoned.
References
- Brewer GJ. The risks of copper toxicity contributing to cognitive decline in the aging population and to Alzheimer's disease. J Am Coll Nutr, 2009;28:238-42.
- Brewer GJ. Risks of copper and iron toxicity during aging in humans. Chem Res Toxicol, 2010;23:319-26.
- Kessler H, Bayer TA, Bach D, et al. Intake of copper has no effect on cognition in patients with mild Alzheimer's disease: a pilot phase 2 clinical trial. J Neural Transm, 2008;115:1181-87.
- Kessler H, Pajonk FG, Meisser P, et al. Cerebrospinal fluid diagnostic markers correlate with lower copper and ceruoloplasmin in patients with Alzheimer's disease. J Neural Transm, 2006;113:1763-69.
- Collins JF, Klevay LM. Copper. Adv Nutr, 2011;2:520-22.
- Walter RM, Uriu-Hare JY, Olin KL, et al. Copper, zinc, manganese, and magnesium status and complications of diabetes mellitus. Diabetes Care, 1991;14:1050-56.
- Zargar AH, Shah NA, Masoodi SR, et al. Copper, zinc, and magnesium levels in non-insulin dependent diabetes. Postgrad Med J, 1998;74:665-68.
- Viktorinova A, Toserova E, Krizko M, Durackova Z. Altered metabolism of copper, zinc, and magnesium is associated with increased levels of glycated hemoglobin in patients with diabetes mellitus. Metab Clin Exp, 2009;58:1477-82.
- Supriya SM, Pinnelli VB, Murgod R. Evaluation of serum copper, magnesium and glycated haemoglobin in type 2 diabetes. Asian J Pharm Clin Res, 2013;6:188-90.
- Aggarwal BB, Shishodia S. Suppression of the nuclear factor-KB activation pathway by spice-derived phytochemicals. An NY Acad Sci, 2002;
- Lim YA, Rhein V, Baysang G, et al. Aß and human amylin share a common toxicity pathway via mitochondrial dysfunction. Proteomics, 2010;10:1621-33.â�©
- Seaman DR. "Antioxidants in Context: Which Supplements to Use and Which to Avoid." MPA Media Webinar on antioxidants.
- Murphy P, Wadiwala I, Sharland DE, Rai GS. Copper and zinc levels in "healthy" and "sick" elderly. J Am Geriatr Soc, 1985;33(12):847-9.
- Meshram A, Agrawal U, Dhok A, Adole P, Meshram K, Khare R. HbA1c, hs-CRP and anthropometric parameters evaluation in the patients of Diabetes Mellitus of Central Rural India. Int J Med Sci Public Health, 2013; 2(2): 293-296.
- Tabak AG, Kivimaki M, Brunner EJ. Changes in C-reactive protein levels before type 2 diabetes and cardiovascular death: the Whitehall II study. Eur J Endocrinol, 2010;163:89-95.
- Morris MC, Evans DA, Tangney CC, et al. Dietary copper and high saturated and trans fat intakes associated with cognitive decline. Arch Neurol, 2006;63:1085-88.
- Seaman DR. Body mass index and musculoskeletal pain: is there a connection? Chiropractic Man Ther, 2013;21:15.
- Seaman DR. Anti-inflammatory diet for pain patients. Pract Pain Management, 2012;12(10)36-46.
- Seaman DR. "When Chronic Inflammation Prevents Success With Manual Care." Dynamic Chiropractic, Aug. 1, 2013.
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