The Linus Pauling Institute says, “Vitamin A and retinoic acid play a central role in the development and differentiation of white blood cells, such as lymphocytes, which play critical roles in the immune response (1).”

Unlike omnivores, vegans do not have a direct, dietary source of vitamin A, but rather get it indirectly via carotenoids (mainly beta-carotene). Beta-carotene is fat-soluble. It seems theoretically, possible then, that a low intake of carotenoids or fat could contribute to lower vitamin A status and white blood cell count (WBC).

This is purely hypothetical; to my knowledge vitamin A levels have not been measured in vegans and other signs of low vitamin A status have not been a noted problem. Anecdotally, I had been eating plenty of beta-carotene and fat at the last measurement of my WBC which showed them to be below normal.

Paul Appleby, of EPIC, passed on a study to me of a clinical trial using a “Daniel Fast” from the University of Memphis (2). In this trial, mostly healthy and some vegetarian subjects (13 men, 30 women; 20-62 years old) went on a Daniel Fast for 21 days, eating no processed or packaged food and only plant foods (as much as they wanted). Their WBC went from an average of 5.7 to 5.0 (2). 5.0 is within the normal range, but on the lower end (normal being about 3.5 to 12.5 billion per liter).

The authors of the Daniel Fast study say, “It has been suggested that ingestion of food additives and preservatives can increase white blood cell count by triggering an immune response due to a sensing of invading pathogens from the food stuff; however, we are unaware of any scientific reports that confirm this hypothesis.” I should point out that lots of things have been suggested, but it doesn’t seem impossible that vegans generally eat less food additives and preservatives and this could be contributing to low WBC.

I have added this information to VeganHealth’s article on White Blood Cells.

There were some other interesting things about this study. Here are the before and after (or during in the case of the nutrient intakes):

calories: 2,185 → 1,722
fat (g): 74 → 54
fat (%): 30 → 27
saturated fat (g): 24 → 9
cholesterol (mg/dl): 171 → 139
LDL (mg/dl): 98 → 76
weight (lbs): 171 → 167
bp: 115/72 → 106/67

The authors did an analysis which showed that the improvements in these parameters did not occur in only the unhealthier subjects, but rather across the board. They say, “It is interesting to note that even those subjects who were vegetarian prior to starting the fast experienced dramatic reductions in total and LDL-[cholesterol], in addition to improvements in other markers. Clearly, the exclusion of meat from the diet (as is the case for vegetarians) is not the only dietary factor involved in raising circulating cholesterol and other risk factors for cardiovascular and metabolic disease.”

It should be noted that this trial had no control group and was not randomized in any way.

I found this interesting because even though the subjects didn’t lose much weight (the weight change wasn’t even statistically significant), their blood pressure and cholesterol levels went down substantially in only 3 weeks. That’s impressive. But does it mean that it is the diet that everyone should be on all the time, indefinitely?

Stay tuned.

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Reference

1. Linus Pauling Institute. Micronutrient Information Center. Vitamin A. Accessed 5/20/13 | link

2. Bloomer RJ, Kabir MM, Canale RE, Trepanowski JF, Marshall KE, Farney TM, Hammond KG. Effect of a 21 day Daniel Fast on metabolic and cardiovascular disease risk factors in men and women. Lipids Health Dis. 2010 Sep 3;9:94. | link

She had been vegan for only 9 months (the report didn’t describe her diet prior to that). She developed gradually worsening paresthesia and tingling of both hands and feet for 6 weeks with a B12 level of 135 pg/ml (normal: 200 – 900) and a mean corpuscular volume of 110 fl (normal: 80-96 fl).

Intravenous B12 therapy was started at 1,000 µg/day for 2 weeks and once weekly thereafter. Complete clinical improvement occurred during two months and two months later there was a striking reduction of the MRI abnormalities.

I’m torn about continuing to blog about these cases because it seems almost gratuitous and I don’t want to bring people down.

Pros:

• It reminds vegan to take their vitamin B12, and each time I publish one of these, some vegans who hadn’t heard this message might hear it for the first time.

• On VeganHealth.org, I tell people to subscribe to my blog or Twitter feed for any changes I make to VeganHealth.org so people know they’re not missing the latest info. (Speaking of which, here is a link to all the non-infant and toddler cases, Individual Cases of Deficiency.)

• I don’t want it to appear like I’m hiding these stories.

Cons:

• It could be unnecessarily annoying or depressing to read these.

In browsing over the recent years, they only come out about one every six months, so it isn’t that often, though sometimes it seems like it.

If you have a strong opinion about this, I’d be interested in knowing. You can tell me not to post your comment (within the comment – they are moderated).

Reference

Gürsoy AE, Kolukısa M, Babacan-Yıldız G, Celebi A. Subacute Combined Degeneration of the Spinal Cord due to Different Etiologies and Improvement of MRI Findings. Case Rep Neurol Med. 2013;2013:159649. doi: 10.1155/2013/159649. Epub 2013 Mar 27. | link

First, a bit of good news from a reader:

“You might be interested to know that since I started following the recommendations in Vegan for Life my depression has all but cleared up (I think mainly as a result of taking 1,000 IU of vitamin D each day as well as a small DHA/EPA supplement). I’ve had depression since I was a child and I can’t tell you how nice it is not to feel miserable all the time. Depression runs in both sides of my family. The fact we live in [city omitted] where it rains nine months of the year doesn’t help matters. So while I still take antidepressants, the change in diet has been a huge boost.”

________________________

An apparently healthy, active, vegan, middle-aged woman contacted me recently saying that she has a low white blood cell count. Her white blood cells were 2.8 billion per liter, while normal is about 3.5 to 10.5 (1), although this can vary depending on the laboratory.

White blood cells are needed to fight foreign invaders, including bacteria, viruses, and cancerous cells. During infections, they typically increase in number. A concise explanation of the various white blood cells, along with some interesting pictures, can be found on this Wikipedia page. One type of white blood cells, eosinophils, can increase during allergic reactions (link), though from what I could find, not enough to significantly effect the total white blood cell count.

Knowing that I also usually have a low white blood cell count (that my doctors have never been very worried about), I got out my old lab reports and here is the history (reference range in parentheses):

1999 – 6.3 (4.0-10.5)
2001 – 2.9 (3.5-12.5)
2002 – 3.2 (3.5-12.5)
2005 – 5.0 (3.5-12.5)
2007 – 3.3 (3.5-12.5)
2008 – 3.3 (4.0-10.5)
2013 – 3.6 (4.3-11.0)

I went vegan in 1988, so the initial, higher number in 1999 was not because I had recently been eating animal products.

The reader who wrote me included a March 2006 article from the Vegetarian Society of Hawaii’s Quarterly Newsletter by William Harris, MD, “Low” WBC counts in vegans (PDF). In the article, Dr. Harris explains that his white blood cell count has been as low as 3.0. He says that Agatha Thrash, MD and Michael Klaper, MD told him that they see many vegans with low white blood cell counts. And if you poke around online, you will find that many vegans have low white blood cells.

Dr. Harris also points out a small amount of research on the topic and I’m afraid there hasn’t been much since then.

The main paper we have to go on is Hadded et al., 1999 (2), which I’ve cited many times for the vitamin B12 and homocysteine information. They also measured white blood cells and found vegans to have an average of 5.0 compared to omnivores who had a count of 5.8 (the difference was statistically significant). As you can see, the vegans’ average white blood cell count of 5.0 falls into the normal range. After considering other immune-related parameters, the authors concluded, “It is not possible to determine from these findings whether the immune status of vegans is compromised or enhanced compared with other groups.”

Dr. Harris goes on to say that “A previous study, Malter M, et al. (3) concluded that ‘Cytotoxic activity…was significantly higher in vegetarians than in their omnivorous controls by a factor of 2. The enhanced natural cytotoxicity may be one of the factors contributing to the lower cancer risk shown by vegetarians.’” That’s good news, but it may not be relevant to those of us with low white blood cells because the abstract points out that in that study, the white blood cells didn’t differ between the vegetarians and non-vegetarians.

I found a 2007 abstract of an article in Polish, in which the researchers found low white blood cells in a group of vegetarians (4), and a 2002 paper in Medical Hypotheses by Mark F. McCarty (5). In it, McCarty says there are several reports that link vegan diets to substantial reductions in white blood cells. He cites Haddad et al. (2) and also a number of other papers, but the only one I could get a copy of was of a clinical trial using a vegetarian diet at a health spa in Norway to treat rheumatoid arthritis (6):

At the beginning of the Norway study, the vegetarian group already had a lower white blood cell count than the control group (about 7.0 vs. 7.5). They fasted on vegetable juice for a week and then ate a gluten-free, vegan diet for 3.5 months after the fast. During the vegan diet, foods higher in protein (seeds and lentils) were added at a rate of one new item every couple days. They then ate a vegetarian diet and were allowed to include dairy products and gluten if they chose. After one month, their white blood cells went down to about 5.5 after which they gradually went back up to 6, where they stayed for the remainder of the year. In this case, a relatively low-protein, vegan diet did not cause white blood cells to drop below the normal range.

The other trials cited by McCarty are listed in footnote 7. I searched PubMed for any other articles measuring vegans’ white blood cells and could not find any.

So why do vegans have lower white blood cell counts than omnivores?

One hypothesis is that we have less of a bacteria, viral, or other toxin load from not eating animal products and, therefore, show lower white blood cells (which typically increase during infections). That seems possible.

Another theory is one put forth by MaCarty who says that IGF-1 plays an important role in the production of white blood cells and that since vegans have lower levels of IGF-1, we have lower levels of white blood cells (5).

There are two things to be concerned about with low white blood cells. The first is infections. If you are a vegan with a low white blood cell count, you know whether you are getting infections easily. I, for one, am not. I’ve only had one cold in going on 2.5 years, and it was very mild. I attribute this to my daily zinc supplementation, but even before I supplemented with zinc, I only got about one cold per year.

The second concern for those of us with white blood cells lower than normal is the possibility of getting cancer. If our white blood cells are low due to lower IGF-1, then our risk of cancer is also possibly lower due to IGF-1 (although the research between IGF-1 and cancer is inconclusive the last I checked). It may be of some solace to know that the only study reporting cancer rates of vegans (for practical purposes), found vegans to have a lower risk (see Take Three: Direct Evidence that Vegans have Lower Cancer Rates).

In summary, we don’t really know why some vegans have lower-than-normal white blood cells, though it does appear to be rather common and not indicative of any obvious problem. If you have a white blood cell count below normal, you should talk to your doctor about whether to be concerned.

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Reference

1. Complete blood count (CBC). Mayo Clinic. Accessed 5/8/2013. | link

2. Haddad EH, Berk LS, Kettering JD, Hubbard RW, Peters WR. Dietary intake and biochemical, hematologic, and immune status of vegans compared with nonvegetarians. Am J Clin Nutr. 1999 Sep;70(3 Suppl):586S-593S. | link

3. Malter M, Schriever G, Eilber U. Natural killer cells, vitamins, and other
blood components of vegetarian and omnivorous men. Nutr Cancer. 1989;12(3):271-8. | link

4. Nazarewicz R. [The effect of vegetarian diet on selected biochemical and blood morphology parameters]. Rocz Panstw Zakl Hig. 2007;58(1):23-7. Polish. | link

5. McCarty MF. Favorable impact of a vegan diet with exercise on hemorheology: implications for control of diabetic neuropathy. Med Hypotheses. 2002 Jun;58(6):476-86. | link

6. Kjeldsen-Kragh J. Rheumatoid arthritis treated with vegetarian diets. Am J Clin Nutr. 1999 Sep;70(3 Suppl):594S-600S. | link

7. Additional clinical trials from McCarty:

Lindahl O, Lindwall L, Spångberg A, Stenram A, Ockerman PA. Vegan regimen with reduced medication in the treatment of bronchial asthma. J Asthma.
1985;22(1):45-55. | link | Not available online. Vegan diet for one year. Abstract doesn’t mention white blood cells.

Lithell H, Bruce A, Gustafsson IB, Höglund NJ, Karlström B, Ljunghall K, Sjölin K, Venge P, Werner I, Vessby B. A fasting and vegetarian diet treatment trial on chronic inflammatory disorders. Acta Derm Venereol. 1983;63(5):397-403. | link | Not available online. Vegan diet for 3 weeks. Abstract does not indicate whether white blood cells decreased.

Schmidt T, Wijga A, Von Zur Mühlen A, Brabant G, Wagner TO. Changes in cardiovascular risk factors and hormones during a comprehensive residential three month kriya yoga training and vegetarian nutrition. Acta Physiol Scand Suppl. 1997;640:158-62. | link | Could not find online.

McCarty also listed the study below (which is the same trial described in Kjeldsen-Kragh et al.’s 1999 paper) saying “see comments”, but I looked up the comments and found nothing about white blood cells.

Kjeldsen-Kragh J, Haugen M, Borchgrevink CF, Laerum E, Eek M, Mowinkel P, Hovi K, Førre O. Controlled trial of fasting and one-year vegetarian diet in rheumatoid arthritis. Lancet. 1991 Oct 12;338(8772):899-902. | link

This new study from France (1) measured ALA levels in the blood, rather than from the diet, and found that higher blood levels of ALA were associated with a reduced risk of late-AMD.

This gives me quite a bit of confidence that the association of ALA with AMD in the Nurse’s Health Study was probably due to confounding. However, we are not out of the woods on yet on AMD and definitely not on cataracts. I hope we know more soon.

You can read more details in the section Eyesight of the VeganHealth.org article, Omega-3 Fatty Acid Recommendations for Vegetarians.

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Reference

1. Merle BM, Delyfer MN, Korobelnik JF, Rougier MB, Malet F, Féart C, Le Goff M, Peuchant E, Letenneur L, Dartigues JF, Colin J, Barberger-Gateau P, Delcourt C. High concentrations of plasma n3 fatty acids are associated with decreased risk for late age-related macular degeneration. J Nutr. 2013 Apr;143(4):505-11. | link

The Bottom Line on Soy and Breast Cancer Risk
August 02, 2012
By Marji McCullough, ScD, RD

Excerpt:

“Bottom line: Even though animal studies have shown mixed effects on breast cancer with soy supplements, studies in humans have not shown harm from eating soy foods. Moderate consumption of soy foods appears safe for both breast cancer survivors and the general population, and may even lower breast cancer risk. Avoid soy supplements until more research is done. So, enjoy your occasional tofu stir-fry or tofu burger – they are unlikely to increase your risk of breast cancer and, on balance, are some of the healthier foods you can eat!”

Warning: There are the typical Weston Price Foundation-type comments after the article – the myths about Asians eating only fermented soy and fermented soy being significantly different than other soy. Too bad they allow comments which will possibly just serve to scare people. And I realize that I’m saying that as someone who allows comments on my own blog, but it’s one thing to be an RD blogger and another to be the strategic director of nutritional epidemiology for the ACS. Of course, that doesn’t mean Dr. McCullough is infallible, but if someone whose opinion is worthwhile has an objection to her article, they can contact the ACS behind the scenes and she can correct the article if they have a valid point. Just my two cents!

(Thanks, Matt.)

While the Huffington Post article was one of many criticizing the Cleveland Clinic study, it was the only one I saw that made any good points. The article is Does Carnitine Really Cause Heart Disease? by Alan Gaby, MD, who is the past president of the American Holistic Medical Association. Towards the very end of the article, Dr. Gaby says, “It is noteworthy that the observed association between heart disease and carnitine levels disappeared completely when the researchers corrected for differences in kidney function.”

This is true – when the researchers corrected for a number of conditions, including kidney function and TMAO levels, the association of carnitine with major adverse cardiac events (MACE) disappeared. The researchers used that model to say that it proved that TMAO was the problem, not carnitine, and it didn’t occur to me in my first analysis that perhaps TMAO levels were high simply because the kidneys couldn’t clear the TMAO. After reading Dr. Gaby’s article I downloaded the online supplementary material and found that kidney function did progressively get worse as carnitine levels increased among the subjects, and this trend was statistically significant. So it seems plausible that perhaps the higher TMAO levels were simply a result of poor kidney function. But this is such an obvious possibility that I couldn’t believe the researchers didn’t consider it and perhaps run an unreported model to test for it. I then wrote the corresponding author of the study, Dr. Stanley Hazen, who is out of the office until the end of the month.

But there’s more. On Thursday, I awoke to news that the Cleveland Clinic group of researchers had published yet another study on TMAO! This time, it was on eggs and lecithin (1). In 2011, they had reported that choline can increase TMAO levels and TMAO was associated with the existence of cardiovascular disease in a cross-sectional study (more info). This time, they were testing phosphatidylcholine (lecithin) from eggs to see if it increased TMAO levels. It did.

Then they performed a prospective study much like the one in the carnitine study (maybe even an arm of the same one?) to see if TMAO was associated with more MACE. Once again, people with higher TMAO levels also had poorer kidney function. But even after adjusting for kidney function, TMAO was still significantly associated with MACE (1.43, 1.05–1.94).

That fully adjusted model included age, sex, smoking status, systolic blood pressure, LDL, HDL, diabetes, C-reactive protein, myeloperoxidase, glomerular filtration rate (kidney function), total white-cell count, body-mass index, medications (aspirin, statins, ACE inhibitor, ARB, or beta-blocker), and the extent of disease as seen on angiography. That’s a lot of adjustments some of which might even be too much, dampening the true effect of TMAO.

As things stand, it appears that kidney function is not the cause of high TMAO and that TMAO might, after all, be a significant cause of MACE. Stay tuned – this story is not over.

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Reference

1. Tang WHW, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, Wu Y, Hazen SL. Intestinal Microbial Metabolism of Phosphatidylcholine and Cardiovascular Risk. N Engl J Med 2013(April 25, 2013);368:1575-1584. | link

It is reproduced here:

Fermented Foods

Because bacteria produce vitamin B12 and fermented foods are generally fermented using bacteria, there are many rumors regarding vitamin B12 being in fermented foods. To my knowledge, no vitamin B12-producing bacteria is required for any fermented food and, therefore, any fermented food that contains vitamin B12 does so via contamination. Because the human colon contains vitamin B12-producing bacteria, it is possible for B12-producing bacterial contamination to occur during food preparation, particularly in places that do not have high levels of cleanliness. To my knowledge, no fermented plant food in Western countries has been found to contain relevant amounts of vitamin B12 analogues.

Tempeh

[snip - nothing new, but click here if interested.]

Korean Centenarians

A 2010 paper from Korea (1) showed that Korean centenarians (people who live to be 100 years old) who ate only small amounts of animal products had normal vitamin B12 levels. The researchers measured the B12 content of plant foods using a biological assay and found many of the fermented foods and seaweeds to contain vitamin B12 analogues, which they considered to be active. They determined that the centenarians were getting about 30% of their B12 from plant foods and that it was a physiologically important amount.

This could be the case, especially given that the subjects ate fermented foods at almost every meal, much of which is homemade kimchi that, according to the researchers, is fermented for at least 10 months.

While this study is very interesting, unless kimchi produced in western countries is reliably shown to lower MMA levels, it would not be wise to rely on it as a significant source of vitamin B12.

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Reference
1. Kwak CS, Lee MS, Oh SI, Park SC. Discovery of novel sources of vitamin b(12) in traditional korean foods from nutritional surveys of centenarians. Curr Gerontol Geriatr Res. 2010;2010:374897. doi: 10.1155/2010/374897. Epub 2011 Mar 8. | link

Every once in awhile, I decide to experiment with taking a molecule that vegans have less of just to see if I notice anything from taking it. A couple years ago I took 1,000 mg of taurine for a week and didn’t notice anything.

For a couple reasons, I recently decided to experiment with it again and took it for 32 days at 500 mg/day. I noticed nothing good nor bad and stopped short of taking the full 50 capsules I had purchased.

Does that meant that red meat actually prevents heart disease via it’s carnitine content?

When someone has a heart attack, their carnitine levels become depleted. The meta-analysis showed that supplementing with large doses of carnitine (an optimal dosage of 6-9 g/day, many times more than one could get from eating red meat) can reduce mortality, particularly in the first 5 days after the heart attack.

Ventricular arrhythmias and angina were also reduced, but heart failure and second heart attacks were not. The paper did not show how long these studies lasted – this information might have been included in their on-line charts, but I could not access them. Many of the studies were not double-blinded and there were some other methodological problems, so it’s not even clear whether carnitine does provide a benefit for all of these parameters, though I would not be surprised if the reduction in 5-day post-heart attack mortality holds true.

In any case, this meta-analysis has basically nothing to do with the study on carnitine and TMAO.

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Reference

1. Dinicolantonio JJ, Lavie CJ, Fares H, Menezes AR, O’Keefe JH. L-Carnitine in the Secondary Prevention of Cardiovascular Disease: Systematic Review and Meta-analysis. Mayo Clin Proc. 2013 Apr 15. doi:pii: S0025-6196(13)00127-4. 10.1016/j.mayocp.2013.02.007. [Epub ahead of print] | link