Low Cholesterol Part 1: Stroke and Depression
It’s been so long since I wrote anything, some of you might have been wondering if I had died from low cholesterol. No, I am still here plugging away. But unlike Dr. Michael Greger, whose Latest in Clinical Nutrition: Volume 15 is now out on DVD, I have not been working at a speed that violates Einstein’s theory of relativity.
My post of August 28th, The Winter of Their Discontent, caused quite a firestorm of comments. (Whoops! – I mean it was correlated with a firestorm of comments.) Let’s just say that some people do not care for the suggestion that cholesterol levels could get too low.
I’ve spent much of my nutrition time over the last few weeks checking out links to studies that people posted in their comments, along with many others that I found along the way, and want to share what I have found. But first, I want to clarify a few things.
The question I am trying to answer is: at what point, if any, does total cholesterol become so low that it could impact things such as steroid hormone production or mood in some people? And as a corollary: Is low cholesterol possibly a culprit when it comes to the egg cravings some vegans get?
One thing I have never said, and am not suggesting, is that low LDL cholesterol levels don’t protect against atherosclerosis (or even mortality) and I’m not sure why people have jumped to the conclusion that I am implying this.
Unfortunately, I have not done a good job of documenting the anecdotal reports of vegans who have come to me with problems who also have very low cholesterol. One guy was passing out unless he ate cheese, and his cholesterol levels were about 100 mg/dl. My recollection is that adding plant saturated fat didn’t help him. A few other people have had loss of libido which improved upon adding coconut oil (I don’t know what their cholesterol levels were). Another person with cholesterol of 94 mg/dl was suffering from mild fatigue, headaches, and anxiety. Kristen, the ex-vegan featured in The Winter of Their Discontent, had an irregular menstrual cycle (among other things) and a cholesterol of 95 mg/dl. However, I also know vegans with cholesterol levels below 100 mg/dl who appear to be thriving.
So what do we know about low cholesterol?
Low Cholesterol and Hemorrhagic Stroke
During the 1990s, it became known that cholesterol was associated with mortality in a U-shaped curve. In other words, both high and low cholesterol levels were associated with higher mortality – though much more on the high cholesterol end. At the time, the thinking was that most of the association of higher mortality with low cholesterol was a merely a manifestation of early cancer, poor nutrition from depression, or liver disease and poor nutrition from alcoholism. The remaining cause of increased mortality was thought to be due to an increase in risk for hemorrhagic stroke (which is a much less prevalent form of stroke than the more typical ischemic stroke where a blood vessel to the brain is blocked).
The most recent, comprehensive review I found on low cholesterol and hemorrhagic stroke was a 2013 meta-analysis of prospective studies (1). Among 17 studies, they found that high total cholesterol was associated with a 31% decreased risk of hemorrhagic stroke (.69, 0.59–0.81), although publication bias was detected. The vast majority of these studies adjusted their results for blood pressure and alcohol intake, among other variables. Lower LDL, but not lower HDL, was also associated with an increased risk of stroke.
It should be noted that lowering one’s LDL decreases heart disease risk by so much that you are better off with a low LDL even if it does increase the risk for hemorrhagic stroke. It is also still possible that these studies had confounding variables that could not be fully adjusted.
The authors finish their paper by saying, “Our results remind clinicians to take this caution during intensive lipid-lowering therapy. Further studies are needed to investigate the underlying pathogenesis better, and identify subjects who would benefit most from lowering cholesterol without risk of hemorrhagic stroke.”
With few exceptions, the low cholesterol category was less than about 150 mg/dl; the average cholesterol in the lowest categories was rarely given. I have not taken the time to read each study and see if there is any way to detect trends as to whether the findings were different based on the different cholesterol levels being compared or the level or types of adjustments.
A reader pointed out a study from Korea (2), which was included in the 2013 meta-analysis (1), in which the risk of hemorrhagic stroke disappeared after adjusting for blood pressure.
There were 8,319 people in the lowest cholesterol category of 130 mg/dl or less (average cholesterol not given). The decreased risk of having a hemorrhagic stroke in the fully adjusted model (including blood pressure and alcohol consumption) for every 38.6 mg/dl (1 mmol/l) increase in total cholesterol was 9% (.91, .87-.95).
However, when they broke the cohort into two groups, those with high blood pressure and those with normal blood pressure, the effect did not hold for those with normal blood pressure. There was still a non-significant trend towards lower stroke in those with “medium” cholesterol levels as compared to the lowest category.
They broke the group up even further. Among those with high blood pressure, they stratified the results for gamma glutamyl transferase (GGT) which reflects alcohol consumption. At low concentrations of GGT, low cholesterol was not associated with a higher risk of hemorrhagic stroke among those with high blood pressure.
The researchers conclude, “In effect, low blood cholesterol may act as a marker of the health damaging effects of alcohol, rather than be a cause of hemorrhagic stroke.”
Based on the results from the 2013 meta-analysis, I’m not sure that this one study from Korea can be considered to put to rest the entire question of whether low cholesterol, in itself, can contribute to hemorrhagic stroke. Apparently the authors of the meta-analysis didn’t think so, but I’m actually inclined to think perhaps it does.
In any case, if you have low cholesterol (below 150 mg/dl) and have either high blood pressure or drink alcohol heavily, you should talk to a doctor about your risk for hemorrhagic stroke.
Low Cholesterol and Depression
The most recent, comprehensive report I found was a 2008 review from the journal, Psychiatry (3). They sum up their findings nicely in the introduction:
“A number of investigators have found a possible relationship between low serum cholesterol levels and mood disorders. In addition, low serum cholesterol levels have been associated with suicidal ideation [suicidal thoughts] and suicide attempts. While the pathophysiology of this association remains unknown, some researchers have postulated that there may be a relationship between altered lipid metabolism and changes in serotonin functioning. In addition, some researchers have found that the pharmacological treatment of depression results in increased serum cholesterol levels. While controversies and inconsistencies characterize this area of study, it appears reasonable to conclude the following: (a) alterations in lipid metabolism may be one of several risk factors for the subsequent development of depression and/or suicidal ideation/suicide attempts (i.e., a non-specific contributory variable) and/or (b) low serum cholesterol levels are an inconsistent but possible biological marker for the manifestation of these phenomena in some individuals.”
In other words, low cholesterol might cause depression and suicidal thoughts/attempts in some individuals. Could this be related to why some ex-vegans claim their mood became much improved upon going back to eating animal products?
More research is needed. Stay tuned for Part II (now available).
1. Wang X, Dong Y, Qi X, Huang C, Hou L. Cholesterol levels and risk of hemorrhagic stroke: a systematic review and meta-analysis. Stroke. 2013 Jul;44(7):1833-9. doi: 10.1161/STROKEAHA.113.001326. Epub 2013 May 23. | link
2. Ebrahim S, Sung J, Song YM, Ferrer RL, Lawlor DA, Davey Smith G. Serum cholesterol, haemorrhagic stroke, ischaemic stroke, and myocardial infarction: Korean national health system prospective cohort study. BMJ. 2006 Jul 1;333(7557):22. Epub 2006 Jun 6. Erratum in: BMJ. 2006 Sep 2;333(7566):468. | link
3. Sansone RA. Cholesterol quandaries: relationship to depression and the suicidal experience. Psychiatry (Edgmont). 2008 Mar;5(3):22-34. | link