Calcium supplements and dementia

Alzheimer's, cardiovascular, and other chronic diseases; biomarkers, lifestyle, supplements, drugs, and health care.
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Stavia
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Calcium supplements and dementia

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https://www.aan.com/PressRoom/home/PressRelease/1487
According to a new study, calcium supplements may be associated with an increased risk of dementia in older women who have had a stroke or other signs of cerebrovascular disease. The research is published in the August 17, 2016, online issue of Neurology[REGISTERED SIGN], the medical journal of the American Academy of Neurology. Cerebrovascular disease is a group of disorders that affect blood flow in the brain. These diseases, including stroke, are the fifth leading cause of death in the United States and increase the risk of developing dementia. “Osteoporosis is a common problem in the elderly. Because calcium deficiency contributes to osteoporosis, daily calcium intake of 1000 to 1200 mg is recommended. Getting this recommended amount through diet alone can be difficult, so calcium supplements are widely used,” said study author Silke Kern, MD, PhD with the University of Gothenburg in Sweden. “Recently, however, the use of supplements and their effect on health has been questioned.” The study involved 700 dementia-free women between the ages of 70 and 92 who were followed for five years. Participants took a variety of tests at the beginning and end of the study, including tests of memory and thinking skills. A CT brain scan was performed in 447 participants at the start of the study. Scientists also looked at the use of calcium supplements in the participants and whether they were diagnosed with dementia over the course of the study. A total of 98 women were taking calcium supplements at the start of the study and 54 women had already experienced a stroke. During the study, 54 more women had strokes, and 59 women developed dementia. Among the women who had CT scans, 71 percent had lesions on their brains’ white matter, which is a marker for cerebrovascular disease. The study found that the women who were treated with calcium supplements were twice as likely to develop dementia than women who did not take supplements. But when the researchers further analyzed the data, they found that the increased risk was only among women with cerebrovascular disease. Women with a history of stroke who took supplements had a nearly seven times increased risk of developing dementia than women with a history of stroke who did not take calcium supplements. Women with white matter lesions who took supplements were three times as likely to develop dementia as women who had white matter lesions and did not take supplements. Women without a history of stroke or women without white matter lesions had no increased risk when taking calcium supplements. Overall, 14 out of 98 women who took supplements developed dementia, or 14 percent, compared to 45 out of 602 women who did not take supplements, or 8 percent. A total of six out of 15 women with a history of stroke who took supplements developed dementia, compared to 12 out of 93 women with a history of stroke who did not take supplements. Among the women with no history of stroke, 18 out of 83 who took supplements developed dementia, compared to 33 out of the 509 who did not take supplements. “It is important to note that our study is observational, so we cannot assume that calcium supplements cause dementia,” said Kern. The author also noted that the study was small and results cannot be generalized to the overall population, and additional studies are needed to confirm the findings. Kern noted that calcium from food affects the body differently than calcium from supplements and appears to be safe or even protective against vascular problems.
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Re: Calcium supplements and dementia

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On the same topic, I like this presentation from Dr. Jason Fung. He takes a long look at calcium supplementation and concludes that the evidence for harm is strong, and the evidence of benefits is weak.
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Re: Calcium supplements and dementia

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The cardiovascular link is not new, but I didn't know about the dementia link.
I'd love to here members take on this.

Here's the CVD-calcium link for members who aren't aware of it.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4125316/

In this review, we discuss this evidence, with a particular focus on increased cardiovascular risk with calcium supplements, which we first described 5 years ago. Calcium supplements with or without
Calcium supplements and cardiovascular risk: 5 years on
Mark J. Bolland, Andrew Grey, and Ian R. Reid
Abstract
Calcium supplements have been widely used by older men and women. However, in little more than a decade, authoritative recommendations have changed from encouraging the widespread use of calcium supplements to stating that they should not be used for primary prevention of fractures. This substantial shift in recommendations has occurred as a result of accumulated evidence of marginal antifracture efficacy, and important adverse effects from large randomized controlled trials of calcium or coadministered calcium and vitamin D supplements. In this review, we discuss this evidence, with a particular focus on increased cardiovascular risk with calcium supplements, which we first described 5 years ago. Calcium supplements with or without vitamin D marginally reduce total fractures but do not prevent hip fractures in community-dwelling individuals. They also cause kidney stones, acute gastrointestinal events, and increase the risk of myocardial infarction and stroke. Any benefit of calcium supplements on preventing fracture is outweighed by increased cardiovascular events. While there is little evidence to suggest that dietary calcium intake is associated with cardiovascular risk, there is also little evidence that it is associated with fracture risk. Therefore, for the majority of people, dietary calcium intake does not require close scrutiny. Because of the unfavorable risk/benefit profile, widespread prescribing of calcium supplements to prevent fractures should be abandoned.
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Re: Calcium supplements and dementia

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Great info. From attending the MPI Cognition physician training, I know that Dr. Bredesen wants his patients’s calcium levels closer to the bottom of the reference range.

FWIW, I fell down the ApoE4/Calcium dysregulation rabbit hole a few months ago after reading the paper below. It may be especially important for our population to pay attention to this.

ApoE4 upregulates the activity of mitochondria-associated ER membranes.
http://www.ncbi.nlm.nih.gov/m/pubmed/26 ... from=apoe4
Abstract
In addition to the appearance of senile plaques and neurofibrillary tangles, Alzheimer's disease (AD) is characterized by aberrant lipid metabolism and early mitochondrial dysfunction. We recently showed that there was increased functionality of mitochondria-associated endoplasmic reticulum (ER) membranes (MAM), a subdomain of the ER involved in lipid and cholesterol homeostasis, in presenilin-deficient cells and in fibroblasts from familial and sporadic AD patients. Individuals carrying the ε4 allele of apolipoprotein E (ApoE4) are at increased risk for developing AD compared to those carrying ApoE3. While the reason for this increased risk is unknown, we hypothesized that it might be associated with elevated MAM function. Using an astrocyte-conditioned media (ACM) model, we now show that ER-mitochondrial communication and MAM function-as measured by the synthesis of phospholipids and of cholesteryl esters, respectively-are increased significantly in cells treated with ApoE4-containing ACM as compared to those treated with ApoE3-containing ACM. Notably, this effect was seen with lipoprotein-enriched preparations, but not with lipid-free ApoE protein. These data are consistent with a role of upregulated MAM function in the pathogenesis of AD and may help explain, in part, the contribution of ApoE4 as a risk factor in the disease.
From my notes:

An exploration of mitochondria-associated ER membrane (MAM) function reveals that calcium is an integral part of this bioenergetic signaling process involving mitochondria. APOE dose-dependently increases intracellular free calcium: E4>E3>E2. APOE-ε4 homozygotes have the MOST intracellular calcium followed by heterozygotes, etc. Mitochondria, the batteries in our cells, don't like too much calcium. Excess intracellular calcium leads to cellular death which may underlie ε4 carriers inherent mitochondrial dysfunction.

Recent studies indicate that impaired contact between MAM and mitochondria might underlie the pathology of several human neurodegenerative diseases, including Alzheimer's disease. Moreover, MAM has been implicated in modulating glucose homeostasis and insulin resistance, as well as in some viral infections.

Magnesium, of course, is the antagonist of calcium. Magnesium deficiency implies an inherent Mg/Ca imbalance. Exploring this lead me to the calcium hypothesis of Alzheimer's disease. I still have lots more to explore here, but suspect that it might be especially important for ε4 carriers to avoid a magnesium deficiency and we may indeed benefit by maintaining higher levels.
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Re: Calcium supplements and dementia

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Aha!! Julie, very very interesting. Do you still take calcium? Last year I recall you did.
I don't.

Calcium metabolism is far more complex than just 1gram intake each day. It's a dynamic pool, with constant movement between the blood and bones, precisely and complexly regulated by various hormones, endocrine organs and kidneys. It's really complex - I had a patient with secondary hyperparathyroidism and calcium imbalance last week, took me days of repeated blood tests and multiple phone calls to the hospital endocrine clinic to sort out.

Short digression:
I was trying to explain to my sister why she shouldn't be swallowing over a gram of calcium tablets in one go, and her answer was "but everyone says if I don't drink milk I won't get enough calcium" and "even orange juice is fortified with calcium".
I then wondered if the dairy and big food industry have pushed the calcium story so hard that everyone has just accepted it unquestioning.
Kinda sounds like the lipid hypothesis huh? ( 'tho the PCSK9 inhibitors do show reduction in CVD events in their pre-market trials so I'm still very open minded there)
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Julie G
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Re: Calcium supplements and dementia

Post by Julie G »

Aha!! Julie, very very interesting. Do you still take calcium? Last year I recall you did.
I don't.
Luckily you have me confused with someone else. I haven't taken them for years. I recall as a young women, my gyn would lecture me on the importance of calcium supplementation at every appt. Taking a daily dose of Tums antacid was highly recommended back in the day. Scary.
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Re: Calcium supplements and dementia

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Excellent!! Very pleased.
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Re: Calcium supplements and dementia

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Stavia wrote:The cardiovascular link is not new, but I didn't know about the dementia link.
I'd love to here members take on this.

Here's the CVD-calcium link for members who aren't aware of it.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4125316/
My recollection of my reading/research at the time of the cardiovascular risk and calcium supplementation link was that it was more likely with non-food calcium over 500 mg daily. I didn't see a discussion of dose effect upon quick scan through the article Stavia posted. So like a good medical provider, I found a study that supports my recollection :D :

The association of calcium supplementation and incident cardiovascular events in the Multi-ethnic Study of Atherosclerosis (MESA)
https://www.ncbi.nlm.nih.gov/pubmed/27514606

The bottom line for me is that supplements have risk for harm. It's hard to find a multi-vitamin without any calcium in it, although interestingly (to me) my Metagenics PhytoMulti does not.
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Re: Calcium supplements and dementia

Post by SusanJ »

Stavia, you're thinking about me. I was taking them as part of the beat osteopenia protocol. I was taking 500 mg in split doses at the time.

We'll see how all the other things I've been doing have helped when I do my next Dexa in December. With my chronic issue of not being able to get my estrogen levels up, I can't say I'm overly optimistic at this point, but I'm fighting the good fight.
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Re: Calcium supplements and dementia

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Aha Susan. Yup. I've negotiated 500mg cut in half twice a day with food for my sister. I've just finished cutting up a huge bottle for her ;)
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